Sensitive Biological Systems Research Articles

An approach to quantify depth-resolved marine photochemical fluxes using remote sensing: Application to carbon monoxide (CO) photoproduction

This paper presents a model to calculate depth-resolved marine photochemical fluxes from remotely sensed ocean color and modeled solar irradiance. The basic approach uses three components: 1) below-sea-surface spectral downward scalar irradiance calculated from a radiative transfer model (STAR) and corrected for clouds using TOMS UV reflectivities; 2) surface-ocean spectral diffuse attenuation coefficients and absorption coefficients for chromophoric dissolved organic matter retrieved from SeaWiFS ocean color using the Sea UV/SeaUVc algorithms; and (3) spectral apparent quantum yield for the photochemical reaction considered. The output of the model is a photochemical rate profile, Ψ PR ( z), where z represents depth. We implemented the model for carbon monoxide (CO) photochemistry using an average apparent quantum yield spectrum and generated a monthly climatology of depth-resolved CO photoproduction rates in the global ocean. The climatology was used to compute global budgets and investigate the spatial and seasonal variabilities of CO photoproduction in the ocean. The model predicts a global CO photoproduction rate of about 41 TgC yr − 1 , in good agreement with other recent published estimates ranging from 30 to 84 TgC yr − 1 . The fate of photochemically derived CO and its role in global biogeochemical cycles remains uncertain however, with biological consumption and sea–air exchange competing for its removal in the surface ocean. Knowledge of the vertical distribution of CO photoproduction is critical in the quantification of the relative magnitudes of these sink mechanisms. The depth-resolution capabilities of this model, together with US Naval Research Laboratory climatology for mixed layer depths allowed further estimation that > 95% of the total water-column CO photoproduction occurs within the mixed layer on a global, yearly basis. Despite this compelling figure, the model also suggests significant spatio-temporal variability in the vertical distribution of CO photoproduction in the subtropical gyres, where up to 40% of water-column CO can be produced below the mixed layer during summertime. While the approach can be applied to other photochemical fluxes (e.g. DIC formation or DMS removal), accurate quantification of such processes with remote sensing will be limited until the mechanisms regulating observed oceanic variability in the apparent quantum yields are better understood. Minor modification to this model can also make it applicable for the determination of the effects of UV and visible solar radiation on sensitive biological systems.

164 DEVELOPMENT OF MURINE EMBRYOS AFTER INJECTION OF UNCOATED GOLD AND SILVER NANOPARTICLES

Novel techniques such as ultrashort pulsed laser technology to produce in situ bio-conjugated nanoparticles (NP) as biomarkers for optical imaging and intervention hold great potential to observe dynamic processes in gametes and embryos without affecting their developmental potential. With regard to toxicology, current preliminary evidence is mainly based on specific cell lines and suggests low toxicity for gold NP (GNP), but a higher toxicity for silver NP (SNP), which also possess a considerable antibacterial effect. Little is known about their impact on sensitive biological systems as early mammalian embryos. The present study investigated the potential toxicity of GNP and SNP in murine embryos for the first time. Since the NP were laser-generated, they formed a stable dispersion in water without the need of surface coating, which might have caused additional toxic effects. Approximately 10 pL of a NP díspersion (average NP diameter of 15 nm) containing 50 μg mL-1 of either GNP or SNP were injected into 1 blastomere of 2-cell-stage embryos (n = 93 or 75, respectively), derived from superovulated NMRI mice. Embryos injected with water alone (n = 79) served as controls. Untreated embryos (n = 92) were run as a handling control. Successful NP injection was confirmed using laser scanning confocal microscopy. After treatment, embryos were cultured for 72 h at 37°C and 5% CO2 in KSOM plus 1% BSA. Embryo development was assessed on a daily basis. No abnormal development was observed. The handling controls reached a blastocyst rate of 77.2%. A total of 66.2% of the water-injected embryos developed to blastocysts, compared to 62.4% and 56.0% after injection of GNP and SNP, respectively. Neither 1-way ANOVA nor an additional chi-square test indicated significant differences between treatment groups. In conclusion, these preliminary data indicate that intracytoplasmatic injection of GNP and SNP had no significant impact on embryo development. Further tests, including qRT-PCR of development-relevant genes in blastocysts and transfer of injected embryos into recipient animals to study potential long-term effects, are underway to gain a better understanding of GNP and SNP embryo toxicology. We gratefully acknowledge the support of the Masterrind GmbH Verden and the NBank Niedersachsen.

Revealing system-level correlations between aging and calorie restriction using a mouse transcriptome

Although systems biology is a perfect framework for investigating system-level declines during aging, only a few reports have focused on a comprehensive understanding of system-level changes in the context of aging systems. The present study aimed to understand the most sensitive biological systems affected during aging and to reveal the systems underlying the crosstalk between aging and the ability of calorie restriction (CR) to effectively slow-down aging. We collected and analyzed 478 aging- and 586 CR-related mouse genes. For the given genes, the biological systems that are significantly related to aging and CR were examined according to three aspects. First, a global characterization by Gene Ontology (GO) was performed, where we found that the transcriptome (a set of genes) for both aging and CR were strongly related in the immune response, lipid metabolism, and cell adhesion functions. Second, the transcriptional modularity found in aging and CR was evaluated by identifying possible functional modules, sets of genes that show consistent expression patterns. Our analyses using the given functional modules, revealed systemic interactions among various biological processes, as exemplified by the negative relation shown between lipid metabolism and the immune response at the system level. Third, transcriptional regulatory systems were predicted for both the aging and CR transcriptomes. Here, we suggest a systems biology framework to further understand the most important systems as they age.

Optically sectioned imaging by oblique plane microscopy

This paper describes a new optically sectioning microscopy technique based on oblique selective plane illumination combined with oblique imaging. This method differs from previous selective plane illumination techniques as the same high numerical aperture lens is used to both illuminate and image the specimen. Initial results obtained using fluorescent pollen grains are presented, together with a measurement of the resolution of the system and an analysis of the potential performance of future systems. Since only the plane of the specimen that is being imaged is illuminated, this technique is particularly suited to time-lapse 3-D imaging of sensitive biological systems where photobleaching and phototoxicity must be kept to a minimum, and it could also be applied to image microfluidic technology for lab-on-a-chip, cytometry and other applications.

Revealing System‐level Correlations between Aging and Calorie Restriction using a Mouse Transcriptome

The present study aimed to understand the most sensitive biological systems affected during aging and to reveal the systems underlying the crosstalk between aging and the ability of calorie restriction (CR), to effectively slowdown aging. We collected and analyzed 478 aging- and 586 CR-related mouse genes. For the given genes, the biological systems that are significantly related to aging and CR were examined according to three aspects. First, a global characterization by Gene Ontology (GO) was performed, where we found that the transcriptome (a set of genes) for both aging and CR were strongly related in the immune response, lipid metabolism, and cell adhesion functions. Second, the transcriptional modularity found in aging and CR was evaluated by identifying possible functional modules, sets of genes that show consistent expression patterns. Our analyses using the given functional modules, revealed systematic interactions among various biological processes as exemplified by the negative relation shown between lipid metabolism and the immune response at the system level. Third, transcriptional regulatory systems were predicted for both the aging and CR transcriptome. Here, we suggest a systems-biological framework to further understand the most important systems as they age. This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (NO. 2007-00376).

Computational investigation of fluid dynamics in a recently developed centrifugal impeller bioreactor

Centrifugal impeller bioreactor (CIB) was recently developed for shear sensitive biological systems. To better understand its fluid velocity profile, liquid circulation flow, shear stress, and circulation time distribution (CTD), in this study a computational fluid dynamics (CFD) approach was taken to quantitatively assess the effects of major impeller designing and bioreactor operating parameters on those characteristics. Comparison of the simulated velocity profiles near the impeller tip with the experimental measurement results was carried out, and a good agreement was demonstrated. Based on the simulated circulation flow through the draft tube, a new empirical correlation of the circulation flow ( Q L) with respect to the impeller designing and operating parameters was established. In addition, three distinct circulation cycles were identified and their time distribution was quantified. The above information obtained from the CFD simulation and analysis is helpful to future optimization and scale-up/scale-down of the CIB.

The history of the Memory of Water

'Homeopathic dilutions' and 'Memory of Water' are two expressions capable of turning a peaceful and intelligent person into a violently irrational one,' as Michel Schiff points out in the introduction of his book 'The Memory of Water'. The idea of the memory of water arose in the laboratory of Jacques Benveniste in the late 1980s and 20 years later the debate is still ongoing even though an increasing number of scientists report they have confirmed the basic results. This paper, first provides a brief historical overview of the context of the high dilution experiments then moves on to digital biology. One working hypothesis was that molecules can communicate with each other, exchanging information without being in physical contact and that at least some biological functions can be mimicked by certain energetic modes characteristics of a given molecule. These considerations informed exploratory research which led to the speculation that biological signaling might be transmissible by electromagnetic means. Around 1991, the transfer of specific molecular signals to sensitive biological systems was achieved using an amplifier and electromagnetic coils. In 1995, a more sophisticated procedure was established to record, digitize and replay these signals using a multimedia computer. From a physical and chemical perspective, these experiments pose a riddle, since it is not clear what mechanism can sustain such 'water memory' of the exposure to molecular signals. From a biological perspective, the puzzle is what nature of imprinted effect (water structure) can impact biological function. Also, the far-reaching implications of these observations require numerous and repeated experimental tests to rule out overlooked artifacts. Perhaps more important is to have the experiments repeated by other groups and with other models to explore the generality of the effect. In conclusion, we will present some of this emerging independent experimental work.

Initial interactions in electromagnetic field-induced biosynthesis.

Low frequency electromagnetic (EM) fields induce gene expression, and recent insights into physical interactions of EM fields with model systems suggest a mechanism that could initiate this process. The consistently low thresholds at which EM fields stimulate biological processes indicate that they require little energy. Since it has been shown that such weak fields accelerate electron transfer reactions, they could stimulate transcription by interacting with electrons in DNA to destabilize the H-bonds holding the two DNA strands together. Such a mechanism is consistent with the low electron affinity of the bases in previously identified electromagnetic response elements (EMREs) needed for EM field interaction with DNA. It is also in line with both endogenous and in vitro stimulation of biosynthesis by electric fields. The frequency response of several EM sensitive biological systems suggests that EM fields require repetition and are most effective at frequencies that coincide with natural rhythms of the processes affected.

Polyphenols and red wine as antioxidants against peroxynitrite and other oxidants.

The antioxidant capacity of polyphenols (+)-catechin, (-)-epicatechin and myricetin, and of different types of red wines (Cabernet Sauvignon, Malbec and blended wine) was evaluated by three assays. (a) NADH oxidation by peroxynitrite (ONOO-): the ONOO- scavenging activity was higher for myricetin (IC50=35 microM) than for (+)-catechin (IC50=275 microM) and (-)-epicatechin (IC50=313 microM). (b) Peroxynitrite initiated chemiluminescence in rat liver homogenate: (-)-epicatechin (IC50=7.0 microM) and (+)-catechin (IC50=13 microM) were more potent than myricetin (IC50=20 microM) in inhibiting the chemiluminescence signal. (c) Lucigenin chemiluminescence in aortic rings: (-)-epicatechin (IC50=15 microM) and (+)-catechin (IC50=18 microM) showed higher antioxidant capacity than myricetin (IC50=32 microM). All the assayed red wines were able to scavenge the oxidants and free radical species that generate the signal in each assay. Cabernet Sauvignon was the red wine with the highest antioxidant capacity in comparison with Malbec and blended wine. It is concluded that the use of sensitive biological systems (as the aortic ring chemiluminescence) provides important information in addition to the results from chemical (NADH oxidation by peroxynitrite) and biochemical (homogenate chemiluminescence) assays and offers advances in the physiological role of polyphenols.

Secondary radiation environments in heavy space vehicles and instruments

Secondary radiations produced by the interactions of primary cosmic rays and trapped protons with spacecraft materials and detectors provides an important, and sometimes dominant, radiation environment for sensitive scientific instruments and biological systems. In this paper the success of a number of calculations in predicting a variety of effects will be examined. The calculation techniques include Monte Carlo transport codes and semi-empirical fragmentation calculations. Observations are based on flights of the Cosmic Radiation Environment and Activation Monitor at a number of inclinations and altitudes on Space Shuttle. The Shuttle experiments included an active cosmic-ray detector as well as metal activation foils and passive detector crystals of sodium iodide which were counted for induced radioactivity soon after return to earth. Results show that cosmic-ray secondaries increase the fluxes of particles of linear energy transfer less than 200 MeV/(gm cm −2), while the activation of the crystals is enhanced by about a factor of three due to secondary neutrons. Detailed spectra of induced radioactivity resulting from spallation products have been obtained. More than a hundred significant radioactive nuclides are included in the calculation and overall close agreement with the observations is obtained.

Picosecond synchrotron radiation pulse radiolysis

This article discusses pulse radiolysis using synchrotron radiation from the TRISTAN accelerators, the accumulation ring (AR) and the main ring (MR). They provide intense radiation, the energy of which goes up to the γ-ray region, and a pulse length below 50 ps, which could be below 10 ps. The time separation between neighboring bunches is 1.25 μs at the AR and 5 μs at the MR. These features should make it possible to detect reactive intermediates in radiation-induced reactions in the time span from picoseconds to microseconds. Possible applications of the picosecond synchrotron radiation pulse radiolysis are introduced. They include studies of radiation effect on resist materials, on radiation sensitive materials, biological systems, and reaction from selected states such as Rydberg state, inner-shell excited states, and multi-ionized states.

The RBE of the leakage radiation from the Hiletron neutron therapy unit

The RBE of the leakage radiation from the Hiletron 14.7 MeV neutron therapy unit has been measured using three sensitive biological systems in mice, which differ markedly in their radiobiological characteristics. These systems comprise type A spermatogonia and bone marrow stem cells, which are affected insignificantly by dose rate, and pigment abnormalities in hair follicles which are affected markedly by dose rate. For mice irradiated at 10 cm depth in a water phantom, the leakage radiation up to 40 cm from the beam axis was virtually as effective as the primary beam for the latter two biological systems, and for spermatogonia in mice when irradiated in air. At this distance, the total dose rate was about 0.2 cGy (rad) per minute (3% of that in the primary beam), and the gamma-ray component was about 70%. This equal effectiveness of the total dose for all three systems was considered fortuitous, and it implied high RBE values for equal effect with the small neutron component at far distances. Considering published data on RBE versus neutron energy, the evidence suggested either a positive interaction of neutron and gamma-ray components in killing bone marrow stem cells when the neutron component was less than 40% of the total dose, or an increased efficiency of neutrons when delivered at very low dose rates. However the components were additive in killing spermatogonia.

The suitability of negative pions for radiotherapy: 4 years preclinical research with the biomedical PiE3-beam at SIN.

The radiobiological experiences over 4 years research with the biomedical pion channel of the 590 MeV proton-accelerator of the Swiss Institute for Nuclear Research (SIN) have been summarized. Mainly sensitive biological systems have been chosen (limiting factor: dose-rate not more than 10 rad/min, exceptionally till 30 rad/min). The RBE values in the peak region vary between 0.7-3.3 and in the plateau region between 0.4-1. The gain factors for pion radiotherapy of cancer are, beside the excellent physical dose distribution, irradiation in the same treatment with two types of radiation: sparsely ionizing (low LET) radiation in plateau (healthy tissue) region and densely ionizing (high LET) radiation in peak (tumor) region. The biological effectiveness ratio in peak and plateau as the clinically most important relation vary between 1.4-4.2. This is valid also for clinically limiting factors such as reaction of skin, of small intestine, vascular damage, dominant lethals in hypoxic cells, tumor induction. For peak pions the RBE in hypoxic cells (tumor cells) can be much higher than in euoxic cells (healthy tissue). This preclinical work supports the hope in a highly effective cancer therapy with negative pions.

SOLAR DOSIMETRY WITH REPAIR DEFICIENT BACTERIAL SPORES: ACTION SPECTRA, PHOTOPRODUCT MEASUREMENTS AND A COMPARISON WITH OTHER BIOLOGICAL SYSTEMS

Abstract— Populations of radiation sensitive spores (Bacillus subtilis UVSSP), vegetative bacteria (E. coli K12‐AB2480) and bacteriophage (E. coli phage T4vx) have been considered as possible biological dosimeters to integrate DNA‐absorbed solar energy incident on the Earth's surface.Irradiation of spores of B. subtilis UVSSP with monochromatic far‐ and near‐UV radiation and solar radiation have indicated that these radiations have a similar efficiency in inducing spore photoproducts per lethal event. Action spectra for lethality taken with the three radiation sensitive biological systems show a similar pattern in each case with a broad shoulder in the 334–365 nm wavelength region. This finding indicates a relatively high susceptibility of the DNA to chemical alteration in this wavelength range. Although less sensitive to sunlight than the other biological systems tested, the B. subtilis UVSSP spore mutant has the advantage of temperature independence of inactivation, stability between irradiation and assay and a simple, reproducible irradiation and assay procedure. Field measurements have supported the utility of this mutant as a sunlight dosimeter.

127-I]- or carrier-free [125-I]monoiodoinsulin

Insulin was enzymatically moniodinated with 127-I or 125-I, and an improved method of purification by anion exchange chromatography was employed. (127-I)Monoiodoinsulin was identified by spectrophotometric analysis and its molar extinction coefficient determined to be 6.31 times 10-3 M-1 cm minus 1. The observed specific activity of carrier-free (125-I)monoidoinsulin was close to the theoretical value (378mCi/mg). The monoiodotyrosyl residue of monoidoinsulin was shown to be solvent-exposed. The ionic properties of the substituted hormone were altered at pH values close to the pK of monoiodotyrosine (8.85), but the pI was unchanged (5.65). (127-I)Monoiodoinsulin formed rhombohedral crystals and co-crystallized with native insulin. Monoidoinsulin was indistinguishable from insulin with respect to binding to two out of three guinea pig anti-insulin sera, to binding to IM9 cultured human lymphocytes, and to binding to isolated rat hepatocyte plasma membranes. The potency of monoidoinsulin was not statistically different from that of insulin in the rat fat cell bioassay and in the mouse convulsion assay. An insulin-degrading enzyme extracted from rat liver degraded monoiodoinsulin less readily than native insulin; monoiodoinsulin was a competitive inhibitor of insulin degradation, and the Km values were 30 nM AND 78 NM for monoidoinsulin and native insulin, respectively. It is concluded that monoidination does not markedly alter the three-dimensional structure of the molecule and that only a few sensitive biological systems are able to distinguish the monoidinated from the native hormone.

Design of Sensitive Photographic Materials for the High-Voltage Electron Microscope

Effective application of the high-voltage electron microscope to a wide variety of biological studies has been restricted by the radiation sensitivity of biological systems. The problem of radiation damage has been recognized as a serious factor influencing the amount of information attainable from biological specimens in electron microscopy at conventional voltages around 100 kV. The problem proves to be even more severe at higher voltages around 1 MV. In this range, the problem is the relatively low sensitivity of the existing recording media, which entails inordinately long exposures that give rise to severe radiation damage. This low sensitivity arises from the small linear energy transfer for fast electrons. Few developable grains are created in the emulsion per electron, while most of the energy of the electrons is wasted in the film base.

Periodische Anregung und Messung schneller chemischer Reaktionen

AbstractRelaxation methods have been developed for the study of fast chemical reactions. With these methods chemical equilibrium is disturbed by a rapid change of temperature, pressure, intensity of light or radiation etc. The following equilibration process is observed by changes of absorption, fluorescence, conductivity etc. The feasibility of relaxation measurements depends on the signal‐to‐noise‐ratio s/n of the signal by which the course of reaction is recorded. The large bandwidth which is necessary to record fast reaction signals causes a high noise level i.e. a poor s/n‐ratio. This disadvantage may be avoided if the perturbation is periodically performed by a rapid change of temperature, pressure, intensity of light or radiation. Thus, the high contents of information contained in periodic signals may be evaluated to increase s/n‐ratio.Owing to this enhancement in s/n‐ratio reactions are measurable which are not detectable at all with a single process. On the other hand, at small excitation energies the relaxation method can be applied also to sensitive biological systems. Furthermore, the time resolution can be improved, too. The periodic chemical relaxation method was developed first for the study of fast photochemical reactions 10−5…10−1 sec) which were excited by short flashes of light and measured by absorption changes. The periodic measuring signal (exciting frequency νa = 2 … 100 c/s) is slowly sampled and recorded in the time T5 (min … h). The gain in s/n‐ratio is given by the expression νa·Ts. An improvement of 200 in s/n‐ratio was attained.—The periodic relaxation method was used to study photochemical reactions which occur during the primary process of photosynthesis.

Distribution and Retention of Plutonium-239 and Neptunium-237 in the Rat Adrenal

The deposition of several radionuclides in the adrenal gland and the apparent lack of sensitivity of this organ to prolonged radiation from internal emitters has been reported by Rhoades (1). The microscopic distribution of plutonium deposited in the adrenal is referred to briefly in her article. More recently, a number of investigators have employed advanced histochemical and biochemical techniques to demonstrate adrenal malfunction after both external and internal radiation exposure. As a rule, the radiation has not been confined to the adrenal per se, and the adrenal deposition has not represented a major fraction of the total body burden of radionuclide. In view of the varied functional role of the adrenal and the sensitivity of biological systems to adrenal secretions, it is conceivable that even low levels of internal adrenal radiation could be of biological significance. It was of interest, therefore, to observe that detectable amounts of Pu239 and Np237 were retained in rat adrenals after administration of fairly massive doses of these radionuclides. A brief description of the retention and zonal distribution of these radioelements in the adrenal gland is presented in this paper.