End-Point Variability Is Not Noise in Saccade Adaptation

When each of many saccades is made to overshoot its target, amplitude gradually decreases in a form of motor learning called saccade adaptation. Overshoot is induced experimentally by a secondary, backwards intrasaccadic target step (ISS) triggered by the primary saccade. Surprisingly, however, no study has compared the effectiveness of different sizes of ISS in driving adaptation by systematically varying ISS amplitude across different sessions. Additionally, very few studies have examined the feasibility of adaptation with relatively small ISSs. In order to best understand saccade adaptation at a fundamental level, we addressed these two points in an experiment using a range of small, fixed ISS values (from 0° to 1° after a 10° primary target step). We found that significant adaptation occurred across subjects with an ISS as small as 0.25°. Interestingly, though only adaptation in response to 0.25° ISSs appeared to be complete (the magnitude of change in saccade amplitude was comparable to size of the ISS), further analysis revealed that a comparable proportion of the ISS was compensated for across conditions. Finally, we found that ISS size alone was sufficient to explain the magnitude of adaptation we observed; additional factors did not significantly improve explanatory power. Overall, our findings suggest that current assumptions regarding the computation of saccadic error may need to be revisited.     

Trace elements in suspended particulate matter from the Yarra River,Australia

Suspended particulate matter (SPM) was collected from two sites in the Yarra River, Australia under a range of flow conditions using a continuous flow centrifuge. The SPM from the upstream, largely rural, site at Warrandyte had higher concentrations of organic matter, phosphorus and manganese. SPM collected from the downstream, largely urban, site at Heidelberg had elevated concentrations of lead and zinc. The concentrations of iron, copper and chromium in the SPM changed little between the two sites.Over the study period, the flow-weighted mean concentration of SPM increased 5-fold between the two sites and the load increased 7-fold. The annual load of SPM transported past Heidelberg was estimated to be 170 000 tonne, with approximately 80% occurring during high flows (> 15 m³ s^-1 ). Detailed study of the SPM concentrations during flood events suggests that the northern tributaries to the Yarra are the main contributors of SPM in the region between Warrandyte and Heidelberg.The mean annual load of total phosphorus transported by the Yarra River at Heidelberg was estimated to be 220 tonne, approximately 2.5 times greater than at Warrandyte. Approximately 60% of this load was associated with SPM. The majority (ca. 80%) of this SPM-bound phosphorus was extractable with 0.1 M NaOH, and is therefore potentially biologically available.There was little difference between the two sites in the flow-weighted mean concentrations of iron, copper and chromium in SPM. The manganese concentration was approximately halved between Warrandyte and Heidelberg, with most of the loss occurring in the exchangeable and reducible fractions. Lead and zinc concentrations in SPM increased 15 to 16-fold between the two sites, with most of this increase occurring in the exchangeable and reducible fractions. This is some cause for concern, since metals in both these fractions could become available to biota under conditions known to exist in the Yarra estuary.     

The Biotechnology Facility for International Space Station

The primary mission of the Cellular Biotechnology Program is to advance microgravity as a tool in basic and applied cell biology. The microgravity environment can be used to study fundamental principles of cell biology and to achieve specific applications such as tissue engineering. The Biotechnology Facility (BTF) will provide a state-of-the-art facility to perform cellular biotechnology research onboard the International Space Station (ISS). The BTF will support continuous operation, which will allow performance of long-duration experiments and will significantly increase the on-orbit science throughput.     

High resolution measurements of sediment resuspension above an accumulation bottom in a stratified lake

A detailed record of suspended particulate matter (SPM) concentrations in the benthic boundary layer (BBL) 1.5 m above an accumulation bottom and 13.5 m below the surface was obtained from frequent (30 min interval) beam attenuation measurements made with a Sea Tech transmissometer in the main basin of Lake Erken, a moderately deep (mean depth 9 m, maximum depth 21 m) dimictic lake in central Sweden. Concentrations of SPM (g m^–3) were not as strongly correlated to the beam attenuation coefficient (c, [m^–1]), as were concentrations of the inorganic SPM fraction. Apparently, this was caused by large optically inactive organic particles which significantly affected the measurements of SPM, but had little effect on the attenuation of light.When the water column was thermally stratified, SPM concentrations in the BBL showed a seasonal increase which was related to an increase in the thermocline depth. As the epilimnion deepened, there was also a marked increase in the occurrence of rapid and large changes in SPM concentration. After the loss of stratification, the amount of SPM and the temporal variability in its concentration was reduced. Since surface waves could not influence sediment resuspension at the depth of measurement, these data show the importance of internal waves in promoting sediment resuspension in areas of sediment accumulation. The relatively short period in each summer, when the thermocline reaches a sufficient depth to allow for resuspension over accumulation bottoms, can have important consequences for both the redistribution of lake sediments and the internal loading of phosphorus.     

Application of a kinetic model to demonstrate how selective feeding could alter the amount of cadmium accumulated by the blue mussel (Mytilus trossolus)

Filter-feeding bivalves are well adapted to a changing food environment, capable of a highly selective feeding strategy. This feeding behaviour results in the rejection of unwanted material as pseudofeces. To assess the importance of a selective feeding behaviour performed by filter-feeding bivalves in influencing amounts of metal accumulated by bivalves, we applied a kinetic model of metal accumulation modified to incorporate feeding behaviour defined as (1) the sorting efficiency (SEF; the ability of the mussel to select organic matter (OM) over inorganic matter (IM) from suspended particulate matter (SPM) cleared from the water column) and (2) rate of rejection of unwanted SPM as pseudofeces (PF). Predicted mussel Cd concentrations (Cd_muss) were compared with Cd_muss predicted without incorporating feeding behaviour as well as to observed Cd_muss. SEF was important at an SPM quality greater than 10% OM; PF production was important at an SPM quantity greater than 3.5 mg l⁻¹ with the influence of PF production on predicted Cd_muss increasing with increasing SPM concentration. Our results suggest that a selective feeding behaviour and the generation of pseudofeces could influence amounts of metal ingested, especially under conditions where SPM quality and quantity are highly variable. Under conditions of high SPM, the influence of SEF and PF production on final Cd_muss should be taken into consideration.     

Efficient insertional mutagenesis in lactococci and other gram-positive bacteria.

In lactococci, the study of chromosomal genes and their regulation is limited by the lack of an efficient transposon mutagenesis system. We associated the insertion sequence ISS1 with the thermosensitive replicon pG+ host to generate a mutagenic tool that can be used even in poorly transformable strains. ISS1 transposition is random in different lactococcal strains as well as in Enterococcus faecalis and Streptococcus thermophilus. High-frequency random insertion (of about 1%) obtained with this system in Lactococcus lactis allows efficient mutagenesis, with typically one insertion per cell. After ISS1 replicative transposition, the chromosome contains duplicated ISS1 sequences flanking pG+ host. This structure allows cloning of the interrupted gene. In addition, efficient excision of the plasmid leaves a single ISS1 copy at the mutated site, thus generating a stable mutant strain with no foreign markers. Mutants obtained by this transposition system are food grade and can thus be used in fermentation processes.     

Oral clonidine provocative test in the diagnosis of growth hormone deficiency in childhood: should we make the timing uniform?

INTRODUCTION: Oral clonidine is one of the most frequent drugs used for the diagnosis of growth hormone deficiency (GHD), but the duration of the test, depending on which European centres use it, is not uniform and can vary from 120 to 150 min or even 180 min. SUBJECTS AND METHODS: To standardize this test, evaluating the possibility to shorten it to 90 min, we investigated the response of GH to the oral clonidine test in 291 children evaluated for short stature (height <-2 SD). Of these, 164 were diagnosed as idiopathic short stature (ISS) and 127 as GHD. In these patients, we calculated: (1) the frequency distribution of the GH peaks to clonidine in GHD and in ISS at various times; (2) the percentage of GH peaks to clonidine before and after 90 min in all and in ISS children; (3) the percentage of the first GH value >or=10 ng/ml before 90 min and after 90 min in ISS. RESULTS: GH peak distribution varied between 30 and 180 min, even though the vast majority of peaks occurred between 30 and 60 min. There was no significant difference (p > 0.05) in the peak distribution between ISS and GHD children. The percentages of GH peaks within 90 min were 92.1% in all children and 95.7% in ISS. If considering the first value of GH >or=10 ng/ml this last percentage reaches 96.3%. CONCLUSION: Our study suggests that the oral clonidine test can be administered for only 90 min without significantly changing its validity. This test should be standardized at 90 min in European protocols just as in those currently used in the USA in order to reduce the discomfort of patients and the cost of this diagnostic procedure.     

Exome sequencing and arrayCGH detection of gene sequence and copy number variation between ILS and ISS mouse strains

It has been well documented that genetic factors can influence predisposition to develop alcoholism. While the underlying genomic changes may be of several types, two of the most common and disease associated are copy number variations (CNVs) and sequence alterations of protein coding regions. The goal of this study was to identify CNVs and single-nucleotide polymorphisms that occur in gene coding regions that may play a role in influencing the risk of an individual developing alcoholism. Toward this end, two mouse strains were used that have been selectively bred based on their differential sensitivity to alcohol: the Inbred long sleep (ILS) and Inbred short sleep (ISS) mouse strains. Differences in initial response to alcohol have been linked to risk for alcoholism, and the ILS/ISS strains are used to investigate the genetics of initial sensitivity to alcohol. Array comparative genomic hybridization (arrayCGH) and exome sequencing were conducted to identify CNVs and gene coding sequence differences, respectively, between ILS and ISS mice. Mouse arrayCGH was performed using catalog Agilent 1 × 244 k mouse arrays. Subsequently, exome sequencing was carried out using an Illumina HiSeq 2000 instrument. ArrayCGH detected 74 CNVs that were strain-specific (38 ILS/36 ISS), including several ISS-specific deletions that contained genes implicated in brain function and neurotransmitter release. Among several interesting coding variations detected by exome sequencing was the gain of a premature stop codon in the alpha-amylase 2B (AMY2B) gene specifically in the ILS strain. In total, exome sequencing detected 2,597 and 1,768 strain-specific exonic gene variants in the ILS and ISS mice, respectively. This study represents the most comprehensive and detailed genomic comparison of ILS and ISS mouse strains to date. The two complementary genome-wide approaches identified strain-specific CNVs and gene coding sequence variations that should provide strong candidates to contribute to the alcohol-related phenotypic differences associated with these strains.     

Plants in space

Virtually all scenarios for the long-term habitation of spacecraft and other extraterrestrial structures involve plants as important parts of the contained environment that would support humans. Recent experiments have identified several effects of spaceflight on plants that will need to be more fully understood before plant-based life support can become a reality. The International Space Station (ISS) is the focus for the newest phase of space-based research, which should solve some of the mysteries of how spaceflight affects plant growth. Research carried out on the ISS and in the proposed terrestrial facility for Advanced Life Support testing will bring the requirements for establishing extraterrestrial plant-based life support systems into clearer focus.     

Benchmark studies of the effectiveness of structural and internal materials as radiation shielding for the international space station

Accelerator-based measurements and model calculations have been used to study the heavy-ion radiation transport properties of materials in use on the International Space Station (ISS). Samples of the ISS aluminum outer hull were augmented with various configurations of internal wall material and polyethylene. The materials were bombarded with high-energy iron ions characteristic of a significant part of the galactic cosmic-ray (GCR) heavy-ion spectrum. Transmitted primary ions and charged fragments produced in nuclear collisions in the materials were measured near the beam axis, and a model was used to extrapolate from the data to lower beam energies and to a lighter ion. For the materials and ions studied, at incident particle energies from 1037 MeV/nucleon down to at least 600 MeV/nucleon, nuclear fragmentation reduces the average dose and dose equivalent per incident ion. At energies below 400 MeV/nucleon, the calculation predicts that as material is added, increased ionization energy loss produces increases in some dosimetric quantities. These limited results suggest that the addition of modest amounts of polyethylene or similar material to the interior of the ISS will reduce the dose to ISS crews from space radiation; however, the radiation transport properties of ISS materials should be evaluated with a realistic space radiation field.     

The biological effects of space radiation during long stays in space.

Many space experiments are scheduled for the International Space Station (ISS). Completion of the ISS will soon become a reality. Astronauts will be exposed to low-level background components from space radiation including heavy ions and other high-linear energy transfer (LET) radiation. For long-term stay in space, we have to protect human health from space radiation. At the same time, we should recognize the maximum permissible doses of space radiation. In recent years, physical monitoring of space radiation has detected about 1 mSv per day. This value is almost 150 times higher than that on the surface of the Earth. However, the direct effects of space radiation on human health are currently unknown. Therefore, it is important to measure biological dosimetry to calculate relative biological effectiveness (RBE) for human health during long-term flight. The RBE is possibly modified by microgravity. In order to understand the exact RBE and any interaction with microgravity, the ISS centrifugation system will be a critical tool, and it is hoped that this system will be in operation as soon as possible.     

Automated Instrument for the Fluorescent Treponemal Antibody-Absorption Test and Other Immunofluorescence Tests

An automated diagnostic test instrument and its development program are described. The instrument automates the fluorescent treponemal antibody-absorption test for syphilis to the extent that only 4 hr of technician time is required to conduct approximately 200 tests daily. Evaluation to date suggests its efficacy. In addition, preliminary studies indicate the feasibility of detecting antibodies to Toxoplasma gondii, Plasmodium malariae, and nucleoprotein (antinuclear factor). The instrument would seem to have broad application for routine and research immunofluorescence testing. Two elements comprise the instrument: a slide processor and a microscope attachment. The slide processor is an electro-pneumatically actuated device which automatically feeds special laboratory slides, on which antigen or other reagents are prefixed, through a series of operations which provide reagent application, incubation, washing, drying, and stacking of the finished slides for readout. The instrument provides flexibility in that incubation time and temperature as well as point, sequence, and duration of reagent application can be varied to accommodate a variety of immunofluorescence techniques. The microscope attachment can be fitted to all conventional dark-field fluorescence microscopes and makes possible the reading of three to six slides per minute. The reacted slides from the processor are injected sequentially onto the stage of the microscope by movement of a lever. As injected, slides are automatically in visual focus; fine focus is occasionally required. Scanning of the reacted field is accomplished by means of the normal microscope controls. A buffered glycerol coupling is maintained between the darkfield condenser substage lens and the slide cover glass by means of a pushbutton-actuated feed system.     

A pilot study on the foraging behaviour of heifers in intensive silvopastoral and monoculture systems in the tropics

Intensive silvopastoral systems (ISS) are a sustainable alternative to monoculture systems (MS). The presence of trees and legumes improves animal welfare due to the increased food quality and quantity and the presence of shade while providing a variety of environmental services. As cattle behaviour is greatly affected by environmental conditions, knowledge on the behavioural trade-offs that cattle make to meet their demands while foraging in different grazing systems is important, as this will help us understand the perceived advantages of ISS. This pilot study assessed the behaviour of heifers in an ISS (n=8 heifers) and MS (n=8 heifers) in the Mexican tropics during the dry and rainy seasons, and its relationship with forage availability, mean travelled distance and the temperature humidity index (THI). In both seasons, daily foraging times were longer in the MS than the ISS (P<0.01). The duration of rumination was higher for ISS (P<0.01) and the duration of lying was higher for the dry season (P<0.05). The decrease in foraging times in relation to THI was significantly higher in the ISS than in the MS (mean slope±SE: ISS=−4.64±0.34; MS=−2.34±0.22; t=−14.20, P<0.001). The results suggest that the forage availability and access to shade in the ISS allow cattle to rest longer and increase rumination, whereas cattle in MS spend more time searching for food and foraging at times of the day were the temperatures were higher as a compensatory strategy, which potentially decreases cattle’s welfare and production qualities when compared with the ISS. In conclusion, ISS are likely to generate positive behavioural trade-offs that result in better welfare conditions and higher productive potential.     

Shifting roles of heterotrophy and autotrophy in coral energetics under varying turbidity

Suspended particulate matter (SPM) strongly alters the trophic environment of photosymbiotic aquatic organisms. At high particles loads, phototrophic energy gains can be diminished due to light absorption by suspended particles, and stress from particle abrasion or deposition on tissues. However, energy gains are enhanced if organisms are able to use SPM as a food source. For photosymbiotic benthic suspension feeders, increases in SPM concentrations may require both phototrophic and heterotrophic acclimation to sustain a positive energy balance. This study provides an experimental analysis of the effects of contrasting light and SPM regimes on the energy budget (scope for growth) of two zooxanthellate corals (Goniastrea retiformis and Porites cylindrica). Using a factorial design in a flow-through tank system, corals were exposed for 2 months to shaded and unshaded conditions (equivalent to 3-4 m depth at 4 and 16 mg dry weight SPM l(-1), respectively) and a range of controlled SPM loads with a natural organic content ( approximately 3% w/w). In G. retiformis, rates of particle ingestion were a linear function of SPM concentration within a broad range (1-30 mg dry weight l(-1)). After 2 months of shading, photosynthetic acclimation was significant in G. retiformis, but did not compensate for the reduced light level, as daily respiration exceeded daily photosynthesis. However, in response to the prolonged shading, G. retiformis more than doubled its rate of particle feeding. At high SPM treatments (16 mg dw l(-1)), sediment feeding by this species compensated fully for the 35-47% lower phototrophy in the shaded treatment. Due to both photo- and heterotrophic plasticity, G. retiformis gained tissue and skeletal mass at all experimental levels of light and SPM. In contrast, rates of particle intake by P. cylindrica contributed <10% to the energy budget in shaded and <3% in unshaded conditions. Feeding rates of P. cylindrica were half-saturated at approximately 3 mg dry weight l(-1), and four- to eight-fold lower than those of G. retiformis. Skeletal growth was sustained, but tissue mass and lipid contents declined in shaded and high-SPM treatments, and carbon loss due to shading by SPM was not compensated for by particle feeding. Thus, due to a lack of photo- and heterotrophic plasticity, periods of high turbidity resulted in energy deficiency in P. cylindrica, and high turbidity conditions appeared physiologically unsustainable for this species. This study is the first to show heterotrophic plasticity in a symbiotic coral, and to show that such plasticity can offset stress from high particle loads. It demonstrates that changes in the trophic mode of some coral species are a mechanism for sustaining a positive energy balance in turbid environments, thereby broadening their physiological niche.     

High-throughput quantification of phosphatidylcholine and sphingomyelin by electrospray ionization tandem mass spectrometry coupled with isotope correction algorithm

The choline head group containing phosphatidylcholine (PC) and sphingomyelin (SPM) are major eukaryotic lipid components playing an important role in forming membrane microdomains and serve as precursor of signaling molecules. Both lipids can be monitored by positive ion mode electrospray tandem mass spectrometry using a parent ion scan of m/z 184. Although PC species appear at even m/z and SPM species at odd m/z, there may be a significant overlap of their isotopes. In order to separate PC and SPM species, an isotope correction algorithm was established, which utilizes calculated isotope percentages to correct the measured peak intensities for their isotopic overlap. We could demonstrate that this approach was applicable to correct the isotope overlap resulting from spiked PC and SPM species. Quantification was achieved by addition of different PC and SPM species prior to lipid extraction. The developed assay showed a precision, detection limit and robustness sufficient for routine analysis. Furthermore, an analysis time of only 1.3 min combined with automated data analysis using self-programmed Excel Macros allows high-throughput analysis. In summary, this assay may be a valuable tool for detailed lipid analysis of PC and SPM species in a variety of sample materials.     

Proteins related to lipoprotein profile were identified using a pharmaco-proteomic approach as markers for growth response to growth hormone (GH) treatment in short prepubertal children

Background  

The broad range in growth observed in response to growth hormone (GH) treatment is mainly caused by individual variations in both GH secretion and GH sensitivity. Individual GH responsiveness can be estimated using evidence-based models that predict the response to GH treatment; however, these models can be improved. High-throughput proteomics techniques can be used to identify proteins that may potentially be used as variables in such models in order to improve their predictive ability. Previously we have reported that proteomic analyses can identify biomarkers that discriminate between short prepubertal children with idiopathic short stature (ISS) who show good or poor growth in response to GH treatment. In this study we used a pharmaco-proteomic approach to identify novel factors that correlate with the growth response to GH treatment in prepubertal children who are short due to GH deficiency or ISS. The study included 128 short prepubertal children receiving GH treatment, of whom 39 were GH-deficient and 89 had ISS. Serum protein expression profiles at study start and after 1 year of GH treatment were analyzed using SELDI-TOF. Cross-validated regression and random permutation analyses were performed to identify significant correlations between protein expression patterns and the 2-year growth response to GH treatment.     

Sources of organic matter in Ria Formosa revealed by stable isotope analysis

The aim of this study is to assess the major sources of organic matter for macroconsumers in the Ria Formosa tidal lagoon. The C, S and N isotopic natural abundances of abundant primary producers of particulate organic matter (POM) and Mytilus galloprovincialis muscle and digestive gland were analysed. The chlorophyll a (Chl a), the suspended particulate matter (SPM) and the POM were measured along the Faro-Olhão channel. The range of variation of stable isotope values among primary producers in Ria Formosa was low suggesting difficulties in the assessment of their relative contribution to higher levels of the food web. Chl a values decreased from outer station to inner station, while SPM and POM values increased. The multiple isotope approach illustrates that POM values along the Faro-Olhão channel, may result from a mixture of upland plants, benthic plants and phytoplankton. Mussel values indicate a selective diet of benthic macrophytes and phytoplankton, with the relative proportions of each determined by the location in the channel. During winters, the upland plants may be an important source of organic matter in the inner lagoon while phytoplankton was an important source of organic matter in the outer lagoon.     

Columbus, the European Physiology Modules Facility and CADMOS

Columbus, the European Space Agency (ESA) orbital facility laboratory will be launched in December 2007 and attached to the International Space Station (ISS). In its launch configuration, Columbus includes 4 multi-user facilities: one of them is the European Physiology Modules Facility, also called EPM. The EPM will be devoted to Human Physiology; it will be collocated in the Columbus module with two other physiology racks, i.e. the HRF-1 and HRF-2 American racks (Human Research Facility). CADMOS is part of the French Space Agency, located in Toulouse; it has been designated by the European Space Agency as the Facility Responsible Centre (FRC) for the EPM. As a User Support and Operations Centre, CADMOS main tasks are to help the scientists to prepare and perform their experiments in Space and to monitor operations on the ISS.     

Immunostimulatory DNA pre-priming: a novel approach for prolonged Th1-biased immunity

Immunostimulatory DNA sequences (ISS) have been shown to promote CTL and Th1 immune responses to coinjected antigens. This phenomenon can be attributed to the capacity of ISS to induce the secretion of type-1 cytokines and to up regulate costimulatory ligands on antigen-presenting cells. We hypothesized that ISS administration prior to antigen administration (prepriming), via the mechanisms stated above, would Th1 bias immune responses to subsequently injected antigens for an extended period of time. The data presented show that ISS provide in vivo adjuvant activity for up to 2 weeks after intradermal or intranasal delivery. Furthermore, the results demonstrate that ISS prepriming can induce immune responses that are significantly stronger than with ISS/antigen covaccination. ISS prepriming offers an alternative approach to the traditional use of adjuvants (i.e., antigen/adjuvant coinjection) and expands the potential clinical applications for ISS.     

Physical and biological organ dosimetry analysis for international space station astronauts

In this study, we analyzed the biological and physical organ dose equivalents for International Space Station (ISS) astronauts. Individual physical dosimetry is difficult in space due to the complexity of the space radiation environment, which consists of protons, heavy ions and secondary neutrons, and the modification of these radiation types in tissue as well as limitations in dosimeter devices that can be worn for several months in outer space. Astronauts returning from missions to the ISS undergo biodosimetry assessment of chromosomal damage in lymphocyte cells using the multicolor fluorescence in situ hybridization (FISH) technique. Individual-based pre-flight dose responses for lymphocyte exposure in vitro to gamma rays were compared to those exposed to space radiation in vivo to determine an equivalent biological dose. We compared the ISS biodosimetry results, NASA's space radiation transport models of organ dose equivalents, and results from ISS and space shuttle phantom torso experiments. Physical and biological doses for 19 ISS astronauts yielded average effective doses and individual or population-based biological doses for the approximately 6-month missions of 72 mSv and 85 or 81 mGy-Eq, respectively. Analyses showed that 80% or more of organ dose equivalents on the ISS are from galactic cosmic rays and only a small contribution is from trapped protons and that GCR doses were decreased by the high level of solar activity in recent years. Comparisons of models to data showed that space radiation effective doses can be predicted to within about a +/-10% accuracy by space radiation transport models. Finally, effective dose estimates for all previous NASA missions are summarized.