Ovine brain natriuretic peptide in cardiac tissues and plasma: effects of cardiac hypertrophy and heart failure on tissue concentration and molecular forms

It is well established that lymphoid dendritic cells (DC) play an important role in the immune system. Beside their role as potent inducers of primary T cell responses, DC seem to play a crucial part as major histocompatibility complex (MHC) class II+ "interdigitating cells" in the thymus during thymocyte development. Thymic DC have been implicated in tolerance induction and also by some authors in inducing major histocompatibility complex restriction of thymocytes. Most of our knowledge about thymic DC was obtained using highly invasive and manipulatory experimental protocols such as thymus reaggregation cultures, suspension cultures, thymus grafting, and bone marrow reconstitution experiments. The DC used in those studies had to go through extensive isolation procedures or were cultured with recombinant growth factors. Since the functions of DC after these in vitro manipulations have been reported to be not identical to those of DC in vivo, we intended to establish a system that would allow us to investigate DC function avoiding artificial interferences due to handling. Here we present a transgenic mouse model in which we targeted gene expression specifically to DC. Using the CD 11c promoter we expressed MHC class II I-E molecules specifically on DC of all tissues, but not on other cell types. We report that I-E expression on thymic DC is sufficient to negatively select I-E reactive CD4+ T cells, and to a less complete extent, CD8+ T cells. In contrast, it only DC expressed I-E in a class II-deficient background, positive selection of CD4+ T cells could not be observed. Thus negative, but not positive, selection events can be induced by DC in vivo.     

A Nanophotonic Structure Containing Living Photosynthetic Bacteria

Photosynthetic organisms rely on a series of self‐assembled nanostructures with tuned electronic energy levels in order to transport energy from where it is collected by photon absorption, to reaction centers where the energy is used to drive chemical reactions. In the photosynthetic bacteria Chlorobaculum tepidum, a member of the green sulfur bacteria family, light is absorbed by large antenna complexes called chlorosomes to create an exciton. The exciton is transferred to a protein baseplate attached to the chlorosome, before migrating through the Fenna–Matthews–Olson complex to the reaction center. Here, it is shown that by placing living Chlorobaculum tepidum bacteria within a photonic microcavity, the strong exciton–photon coupling regime between a confined cavity mode and exciton states of the chlorosome can be accessed, whereby a coherent exchange of energy between the bacteria and cavity mode results in the formation of polariton states. The polaritons have energy distinct from that of the exciton which can be tuned by modifying the energy of the optical modes of the microcavity. It is believed that this is the first demonstration of the modification of energy levels within living biological systems using a photonic structure.     

Digital eco-art: transformative possibilities

Abstract

Cave paintings bear witness that, early in human cultural development, art and the means to create it (technology) became a method of expression and translation of human interconnectedness with nature defined as the non-human-made world. Contemporary new media artists interacting with nature through the medium of digital technologies in situ continue this exploration within the genre referred to as “digital eco-art”. LocoMotoArt, an independently powered creative field system, was used as a vehicle for conducting media arts practice in natural settings during a three-year qualitative field research project. Findings indicate that human–technology–nature interconnectedness is a possible conduit for establishing a role for digital technology beyond social networking, computing, information gathering and gaming to engage with nature. We argue that digital eco-artists are at the vanguard of creating a new sense of aesthetic and environmental engagement, proportions of which emerge as transformative possibilities. The art experience of digital eco-art can change from being a contemplative one to a living experience.     

The subunit structure of alpha-acetohydroxyacid isomeroreductase from Salmonella typhimurium

Alpha-Acetohydroxyacid isomeroreductase from Salmonella typhimurium has a native molecular weight of 220,000. The constituent polypeptide chains exhibit anomalous but unimodal electrophoretic migration on sodium dodecyl sulfate-urea polyacrylamide gels. The subunit molecular weight, determined by sedimentation equilibrium in 6 M guanidine hydrochloride, is 57,000. The apparent tetrameric nature of the native enzyme was confirmed by determining the types of oligomers formed upon cross-linking with dimethylsebacimidate. Analysis of tryptic peptides suggests that the polypeptide chains have an identical amino acid sequence. Carbohydrate analysis, ultraviolet absorption spectrum, and atomic absorption spectrum are consistent with the lack of cobalamine and cobalt. The Michaelis constants are as follows: alpha-acetolactate, 2.9 x 10-4 M; alpha-aceto-alpha-hydroxybutyrate, 7.8 x 10-4 M; NADPH, 1.5 x 10-5 M; Mg2+, 7.7 x 10-4 M. The catalytic constants (molecules of substrate catalyzed per min per molecules of enzyme) for alpha-acetolactate and alpha-aceto-alpha-hydroxybutyrate are 1,100 and 4,700, respectively. Comparative tryptic peptide analysis and immunological analysis show that alpha-acetohydroxyacid isomero-reductase and biosynthetic L-threonine deaminase bear no structural relationship and therefore rule out a "shared structure" hypothesis for the putative involvement of L-threonine deaminase in the synthesis of alpha-acetohydroxyacid isomeroreductase.     

Chemical composition of the frontal gland secretion ofSyntermes soldiers (Isoptera,Termitidae)

The defensive secretions from the frontal glands of soldier termites of the genusSyntermes contain similar mixtures of mono- and sesquiterpene hydrocarbons. The major components inS. dirus, S. molestus, S. brevimalatus, S. peruanus, and a new species (Syntermes sp. n), iscis--ocimene. A substantial amount of aristolochene is found inSyntermes sp. n. and is present at lower levels in all the other species;S. brevimalatus contains onlycis--ocimene and aristolochene. The four other species also contain minor amounts of epi--selinene and germacrene A. The latter compound has been identified on the basis of its rearrangement product -elemene. The termiteS. grandis differed markedly from the otherSyntermes species in that no terpenoid components were found in the soldier extract. With the obvious exception ofS. grandis, the same soldier-specific mono- and sesquiterpenes occurred in all species. The total amount of secretion per unit weight of soldiers varies with the species and is inversely proportional to the development of the mandibular apparatus. InS. molestus smaller gland size is compensated for by a greater number of soldiers foraging trails.     

Determination of peak expiratory flow

It is still unknown whether peak expiratory flow (PEF) is determined by "wave speed" flow limitation in the airways. To investigate the influences of airway mechanical properties on PEF, five healthy adults performed maximal forced expiratory effort (MFEE) manoeuvres, in the standard manner and following breathholds at total lung capacity (TLC) of 2 s and 10 s. Oesophageal pressure (Poes) was measured as an index of respiratory effort. Subjects also performed a MFEE following a 10 s breathhold during which intrathoracic pressure was voluntarily raised by a Valsalva manoeuvre, which would increase transmural pressure and cross-sectional area of the extrathoracic airway. Additional MFEEs were performed with the neck fully flexed and extended, to change longitudinal tracheal tension. In separate studies, PEF was measured with a spirometer and with a pneumotachograph. Breathholds at TLC (2 s and 10 s), and neck flexion reduced PEF by a mean of 9.8% (SD 2.9%), 9.6% (SD 1.6%), and 8.7% (SD 2.8%), respectively, when measured with the spirometer. The same pattern of results was seen when measured with the pneumotachograph. These reductions occurred despite similar respiratory effort. Voluntarily raising intrathoracic pressure during a 10 s breathhold did not reverse a fall in PEF. MFEE manoeuvre with neck extension did not result in an increase in PEF, the group mean % changes being -3.0% (SD 5.0%). We conclude that these results do not allow the hypothesis that "wave-speed" (Vws) is reached at PEF to be rejected. A breathhold at TLC could increase airway wall compliance by allowing stress-relaxation of the airway, thus reducing the "Vws" achievable.     

Developmental toxicity evaluation of ethylene glycol by gavage in New Zealand white rabbits

Artificially inseminated New Zealand white (NZW) rabbits were administered ethylene glycol (EG) by gavage on Gestational Days (GD) 6 through 19 at doses of 0, 100, 500, 1000, or 2000 mg/kg/day, with 23-24 inseminated animals per group. Clinical signs were recorded and water consumption was measured daily; does were weighed on GD 0, 6-19, 25, and 30. At necropsy (GD 30), maternal liver, kidney, and gravid uterine weights were recorded. Histopathologic examination was performed on kidneys from 10 does/dose and for all unscheduled deaths. Ovarian corpora lutea were counted and uterine implantation sites (total sites, resorptions, dead and live fetuses) were recorded. All live fetuses were weighed, sexed, and examined for external, visceral, and skeletal malformations and variations. EG resulted in profound maternal toxicity at 2000 mg/kg/day (42% mortality; three early deliveries and one spontaneous abortion) associated with renal pathology and unaccompanied by any other indicators of maternal toxicity. Renal lesions at 2000 mg/kg/day involved the cortical renal tubules and included intraluminal oxalate crystals, epithelial necrosis, and tubular dilatation and degeneration. No dose-related maternal toxicity occurred at 100-1000 mg/kg/day. There was no indication of developmental toxicity at any dose tested, including no effects on pre- or postimplantation loss, number of fetuses, fetal body weight, or sex ratio (% male fetuses) per litter, and no evidence of teratogenicity. The "no observable adverse effect level" (NOAEL) for maternal toxicity was therefore 1000 mg/kg/day and the NOAEL for developmental toxicity was at least 2000 mg/kg/day in this study. The sensitivity of NZW rabbits relative to that of Sprague-Dawley rats and Swiss mice for maternal and developmental toxicity from gavage administration of EG during organogenesis can be determined for maternal toxicity: rabbits > mice > rats, and for developmental toxicity, mice > rats > rabbits.     

Emerging concepts in the Ras superfamily of GTP-binding proteins

The Ras superfamily of GTP-binding proteins (> 50 members) regulates a diverse spectrum of intracellular processes. These include cellular proliferation and differentiation, intracellular vesicular trafficking, cytoskeletal control, NADPH oxidase function, as well as others. In this review, we describe recent progress and emerging themes in the action and regulation of these important cellular regulatory molecules. Structural studies have provided insight into the function of low molecular weight GTP-binding proteins (LMWGs) as molecular switches, and are defining modes of interaction with associated regulatory molecules. Details of the enzymatic processes involved in the posttranslational processing of LMWGs, and how this processing is important for protein function, are being elucidated. A variety of GTPase activating proteins, GDP/GTP dissociation stimulators, and GDP dissociation inhibitors have been identified, and their ability to determine the activity of LMWG-regulated systems is being worked out. The discovery of multifunctional regulatory molecules has indicated that substantial "crosstalk" between various LMWG may occur. The continuing emergence of additional cellular functions that are regulated by LMWGs, and particularly the recent availability of in vitro analytical systems for studies of the mechanism (or mechanisms) of action of LMWGs, is resulting in a wealth of information about the regulation and integration of cellular signaling, form, and function.     

天津市成都道新建村住宅小区

项目背景：本项目位于天津市著名的五大道之一的成都道．是现代城市中心地段的高档高层住宅小区和沿街商业建筑的综合发展项目。建筑单体及总平面设计采用现代风格，设计任务书对景观设计的要求是：设计风格是后现代的．手法和材料是现代的．尽量将传承地域文化的片断融合在设计中。     

Hepatic sequestration and modulation of the canalicular transport of the organic cation, daunorubicin, in the Rat

In contrast to organic anions, substrates for the canalicular mdr1a and b are usually organic cations and are often sequestered in high concentrations in intracellular acidic compartments. Because many of these compounds are therapeutic agents, we investigated if their sequestration could be regulated. We used isolated perfused rat liver (IPRL), isolated rat hepatocyte couplets (IRHC), and WIF-B cells to study the cellular localization and biliary excretion of the fluorescent cation, daunorubicin (DNR). Despite rapid (within 15 minutes) and efficient (>90%) cellular uptake in the IPRL, only approximately 10% of the dose administered (0.2-20 micromol) was excreted in bile after 85 minutes. Confocal microscopy revealed fluorescence predominantly in vesicles in the pericanalicular region in IPRL, IRHC, and WIF-B cells. Treatment of these cells with chloroquine and bafilomycin A, agents that disrupt the pH gradient across the vesicular membrane, resulted in a loss of vesicular fluorescence, reversible in the case of bafilomycin A. Taurocholate (TC) and dibutyryl cAMP (DBcAMP), stimulators of transcytotic vesicular transport, increased the biliary recovery of DNR significantly above controls, by 70% and 35%, respectively. The microtubule destabilizer, nocodazole, decreased biliary excretion of DNR. No effect on secretion was noted in TR- mutant rats deficient in mrp2. Coadministration of verapamil, an inhibitor of mdr1, also decreased DNR excretion. While TC and DBcAMP did not affect the fluorescent intensity or pattern of distribution in IRHC, nocodazole resulted in redistribution of DNR to peripheral punctuate structures. These findings suggest that the organic cation, DNR, is largely sequestered in cells such as hepatocytes, yet its excretion can still be modulated.