Modernizing and Expanding the NASA Space Geodesy Network to Meet Future Geodetic Requirements.

NASA maintains and operates a global network of Very Long Baseline Interferometry (VLBI), Satellite Laser Ranging (SLR), and Global Navigation Satellite System (GNSS) ground stations as part of the NASA Space Geodesy Program. The NASA Space Geodesy Network (NSGN) provides the geodetic products that support Earth observations and the related science requirements as outlined by the US National Research Council (NRC 2010, 2018). The Global Geodetic Observing System (GGOS) and the NRC have set an ambitious goal of improving the Terrestrial Reference Frame (TRF) to have an accuracy of 1 millimeter and stability of 0.1 millimeters per year, an order of magnitude beyond current capabilities. NASA and its partners within GGOS are addressing this challenge by planning and implementing modern geodetic stations co-located at existing and new sites around the world. In 2013, NASA demonstrated the performance of its next-generation systems at the prototype next-generation core site at NASA's Goddard Geophysical and Astronomical Observatory in Greenbelt, Maryland. Implementation of a new broadband VLBI station in Hawaii was completed in 2016. NASA is currently implementing new VLBI and SLR stations in Texas and is planning the replacement of its other aging domestic and international legacy stations. In this article, we describe critical gaps in the current global network and discuss how the new NSGN will expand the global geodetic coverage and ultimately improve the geodetic products. We also describe the characteristics of a modern NSGN site and the capabilities of the next-generation NASA SLR and VLBI systems. Finally, we outline the plans for efficiently operating the NSGN by centralizing and automating the operations of the new geodetic stations.

Evaluation of mammographic surveillance services in women aged 40-49 years with a moderate family history of breast cancer: a single-arm cohort study.

BACKGROUND: Women with a significant family history of breast cancer are often offered more intensive and earlier surveillance than is offered to the general population in the National Breast Screening Programme. Up to now, this strategy has not been fully evaluated. OBJECTIVE: To evaluate the benefit of mammographic surveillance for women aged 40-49 years at moderate risk of breast cancer due to family history. The study is referred to as FH01. DESIGN: This was a single-arm cohort study with recruitment taking place between January 2003 and February 2007. Recruits were women aged < 50 years with a family history of breast or ovarian cancer conferring at least a 3% risk of breast cancer between ages 40 and 49 years. The women were offered annual mammography for at least 5 years and observed for the occurrence of breast cancer during the surveillance period. The age group 40-44 years was targeted so that they would still be aged < 50 years after 5 years of surveillance. SETTING: Seventy-four surveillance centres in England, Wales, Scotland and Northern Ireland. PARTICIPANTS: A total of 6710 women, 94% of whom were aged < 45 years at recruitment, with a family history of breast cancer estimated to imply at least a 3% risk of the disease between the ages of 40 and 50 years. INTERVENTIONS: Annual mammography for at least 5 years. MAIN OUTCOME MEASURES: The primary study end point was the predicted risk of death from breast cancer as estimated from the size, lymph node status and grade of the tumours diagnosed. This was compared with the control group from the UK Breast Screening Age Trial (Age Trial), adjusting for the different underlying incidence in the two populations. RESULTS: As of December 2010, there were 165 breast cancers diagnosed in 37,025 person-years of observation and 30,556 mammographic screening episodes. Of these, 122 (74%) were diagnosed at screening. The cancers included 44 (27%) cases of ductal carcinoma in situ. There were 19 predicted deaths in 37,025 person-years in FH01, with an estimated incidence of 6.3 per 1000 per year. The corresponding figures for the Age Trial control group were 204 predicted deaths in 622,127 person-years and an incidence of 2.4 per 1000 per year. This gave an estimated 40% reduction in breast cancer mortality (relative risk = 0.60; 95% confidence interval 0.37 to 0.98; p = 0.04). CONCLUSIONS: Annual mammography in women aged 40-49 years with a significant family history of breast or ovarian cancer is both clinically effective in reducing breast cancer mortality and cost-effective. There is a need to further standardise familial risk assessment, to research the impact of digital mammography and to clarify the role of breast density in this population. TRIAL REGISTRATION: National Research Register N0484114809. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 11. See the HTA programme website for further project information.

ATP inhibits Ins(1,4,5)P3-evoked Ca2+ release in smooth muscle via P2Y1 receptors.

Adenosine 5'-triphosphate (ATP) mediates a variety of biological functions following nerve-evoked release, via activation of either G-protein-coupled P2Y- or ligand-gated P2X receptors. In smooth muscle, ATP, acting via P2Y receptors (P2YR), may act as an inhibitory neurotransmitter. The underlying mechanism(s) remain unclear, but have been proposed to involve the production of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] by phospholipase C (PLC), to evoke Ca(2+) release from the internal store and stimulation of Ca(2+)-activated potassium (K(Ca)) channels to cause membrane hyperpolarization. This mechanism requires Ca(2+) release from the store. However, in the present study, ATP evoked transient Ca(2+) increases in only ∼10% of voltage-clamped single smooth muscle cells. These results do not support activation of K(Ca) as the major mechanism underlying inhibition of smooth muscle activity. Interestingly, ATP inhibited Ins(1,4,5)P(3)-evoked Ca(2+) release in cells that did not show a Ca(2+) rise in response to purinergic activation. The reduction in Ins(1,4,5)P(3)-evoked Ca(2+) release was not mimicked by adenosine and therefore, cannot be explained by hydrolysis of ATP to adenosine. The reduction in Ins(1,4,5)P(3)-evoked Ca(2+) release was, however, also observed with its primary metabolite, ADP, and blocked by the P2Y(1)R antagonist, MRS2179, and the G protein inhibitor, GDPßS, but not by PLC inhibition. The present study demonstrates a novel inhibitory effect of P2Y(1)R activation on Ins(1,4,5)P(3)-evoked Ca(2+) release, such that purinergic stimulation acts to prevent Ins(1,4,5)P(3)-mediated increases in excitability in smooth muscle and promote relaxation.

Analysis of munitions constituents in groundwater using a field-portable GC-MS.

The use of munitions constituents (MCs) at military installations can produce soil and groundwater contamination that requires periodic monitoring even after training or manufacturing activities have ceased. Traditional groundwater monitoring methods require large volumes of aqueous samples (e.g., 2-4 L) to be shipped under chain of custody, to fixed laboratories for analysis. The samples must also be packed on ice and shielded from light to minimize degradation that may occur during transport and storage. The laboratory's turn-around time for sample analysis and reporting can be as long as 45 d. This process hinders the reporting of data to customers in a timely manner; yields data that are not necessarily representative of current site conditions owing to the lag time between sample collection and reporting; and incurs significant shipping costs for samples. The current work compares a field portable Gas Chromatograph-Mass Spectrometer (GC-MS) for analysis of MCs on-site with traditional laboratory-based analysis using High Performance Liquid Chromatography with UV absorption detection. The field method provides near real-time (within ~1 h of sampling) concentrations of MCs in groundwater samples. Mass spectrometry provides reliable confirmation of MCs and a means to identify unknown compounds that are potential false positives for methods with UV and other non-selective detectors.

The phospholipase C inhibitor U-73122 inhibits Ca(2+) release from the intracellular sarcoplasmic reticulum Ca(2+) store by inhibiting Ca(2+) pumps in smooth muscle.

BACKGROUND AND PURPOSE: The sarcoplasmic reticulum (SR) releases Ca(2+) via inositol 1,4,5-trisphosphate receptors (IP(3)R) in response to IP(3)-generating agonists. Ca(2+) release subsequently propagates as Ca(2+) waves. To clarify the role of IP(3) production in wave generation, the contribution of a key enzyme in the production of IP(3) was examined using a phosphoinositide-specific phospholipase C (PI-PLC) inhibitor, U-73122. EXPERIMENTAL APPROACH: Single colonic myocytes were voltage-clamped in whole-cell configuration and cytosolic Ca(2+) concentration ([Ca(2+)](cyto)) measured using fluo-3. SR Ca(2+) release was evoked either by activation of IP(3)Rs (by carbachol or photolysis of caged IP(3)) or ryanodine receptors (RyRs; by caffeine). KEY RESULTS: U-73122 inhibited carbachol-evoked [Ca(2+)](cyto) transients. The drug also inhibited [Ca(2+)](cyto) increases, evoked by direct IP(3)R activation (by photolysis of caged IP(3)) and RyR activation (by caffeine), which do not require PI-PLC activation. U-73122 also increased steady-state [Ca(2+)](cyto) and slowed the rate of Ca(2+) removal from the cytoplasm. An inactive analogue of U-73122, U-73343, was without effect on either IP(3)R- or RyR-mediated Ca(2+) release. CONCLUSIONS AND IMPLICATIONS: U-73122 inhibited carbachol-evoked [Ca(2+)](cyto) increases. However, the drug also reduced Ca(2+) release when evoked by direct activation of IP(3)R or RyR, slowed Ca(2+) removal and increased steady-state [Ca(2+)](cyto). These results suggest U-73122 reduces IP(3)-evoked Ca(2+) transients by inhibiting the SR Ca(2+) pump to deplete the SR of Ca(2+) rather than by inhibiting PI-PLC.

Making sense of electrical sense in crayfish.

The five sensory modalities of humans are also found in a wide range of invertebrates. Other vertebrates have evolved additional special senses, such as the magnetic sense, which are also found in some invertebrates. However, there remain a few sensory abilities that curiously appear to be found in either vertebrates or invertebrates, but not both. For example, electrosensitivity - the ability to detect electric fields in water - which should benefit vertebrates and invertebrates alike, is apparently only used by vertebrates. However, recent reports suggest that some invertebrates could have an electric sense. Here we examine that possibility further and demonstrate a behavioural threshold to low-level electrical fields in two freshwater invertebrates. The responses are not low enough for them to detect the Earth's magnetic field as some other electroreceptive species can do, but sufficiently low for them to use in navigation or prey and predator detection. This finding challenges the current view of the sensory world of aquatic invertebrates and has implications for the evolution of this ability.

Regulation by FK506 and rapamycin of Ca2+ release from the sarcoplasmic reticulum in vascular smooth muscle: the role of FK506 binding proteins and mTOR.

BACKGROUND AND PURPOSE: The sarcoplasmic reticulum (SR), regulates the cytoplasmic Ca(2+) concentration ([Ca(2+)](cyto)) in vascular smooth muscle. Release from the SR is controlled by two intracellular receptor/channel complexes, the ryanodine receptor (RyR) and the inositol 1,4,5-trisphosphate receptor (IP(3)R). These receptors may be regulated by the accessory FK506-binding protein (FKBP) either directly, by binding to the channel, or indirectly via FKBP modulation of two targets, the phosphatase, calcineurin or the kinase, mammalian target of rapamycin (mTOR). EXPERIMENTAL APPROACH: Single portal vein myocytes were voltage-clamped in whole cell configuration and [Ca(2+)](cyto) measured using fluo-3. IP(3)Rs were activated by photolysis of caged IP(3) and RyRs activated by hydrostatic application of caffeine. KEY RESULTS: FK506 which displaces FKBP from each receptor (to inhibit calcineurin) increased the [Ca(2+)](cyto) rise evoked by activation of either RyR or IP(3)R. Rapamycin which displaces FKBP (to inhibit mTOR) also increased the amplitude of the caffeine-evoked, but reduced the IP(3)-evoked [Ca(2+)](cyto) rise. None of the phosphatase inhibitors, cypermethrin, okadaic acid or calcineurin inhibitory peptide, altered either caffeine- or IP(3)-evoked [Ca(2+)](cyto) release; calcineurin did not contribute to FK506-mediated potentiation of RyR- or IP(3)R-mediated Ca(2+) release. The mTOR inhibitor LY294002, like rapamycin, decreased IP(3)-evoked Ca(2+) release. CONCLUSIONS AND IMPLICATIONS: Ca(2+) release in portal vein myocytes, via RyR, was modulated directly by FKBP binding to the channel; neither calcineurin nor mTOR contributed to this regulation. However, IP(3)R-mediated Ca(2+) release, while also modulated directly by FKBP may be additionally regulated by mTOR. Rapamycin inhibition of IP(3)-mediated Ca(2+) release may be explained by mTOR inhibition.

CT staging of loco-regional breast cancer recurrence. A worthwhile practice?

AIMS: To assess the usefulness of computed tomography of the chest, abdomen, and pelvis (CTCAP) in the detection of metastatic disease in patients presenting with loco-regional recurrence of breast cancer, and to identify subgroups particularly likely to have metastases. MATERIALS AND METHODS: Over a 32-month period, 63 patients with 65 recurrences underwent CTCAP, and were identified from the hospital's computerized radiology system. RESULTS: Twenty-one patients (32%) had metastases, including bony (n=5, 8%), liver (n=7, 11%), and thoracic disease (n=11, 17%). Patients with recurrence in a conserved breast had lower rates of metastasis on CT than those with other sites of recurrence [three of 21 (14%) versus 18 of 44 (41%), p=0.03]. Patients younger than 50 years at primary diagnosis or younger than 60 years at recurrence had statistically significantly higher rates of metastasis than older patients [10 of 16 (63%) versus 11 of 48 (23%), p=0.003, and 13 of 23 (57%) versus eight of 42 (19%), p=0.002, respectively]. CONCLUSION: CT staging of patients presenting with loco-regional recurrence of breast cancer is a worthwhile practice. Younger patients and those with recurrence other than in the conserved breast are particularly likely to have metastatic disease.

Video tracking in the extreme: video analysis for nocturnal underwater animal movement.

Computer analysis of video footage is one option for recording locomotor behavior for a range of neurophysiological and behavioral studies. This technique is reasonably well established and accepted, but its use for some behavioral analyses remains a challenge. For example, filming through water can lead to reflection, and filming nocturnal activity can reduce resolution and clarity of filmed images. The aim of this study was to develop a noninvasive method for recording nocturnal activity in aquatic decapods and test the accuracy of analysis by video tracking software. We selected crayfish, Cherax destructor, because they are often active at night, they live underwater, and data on their locomotion is important for answering biological and physiological questions such as how they explore and navigate. We constructed recording arenas and filmed animals in infrared light. Wethen compared human observer data and software-acquired values. In this article, we outline important apparatus and software issues to obtain reliable computer tracking.

Exploring with damaged antennae: do crayfish compensate for injuries?

Appendages are important sources of sensory information for all animals that possess them but they are commonly damaged in nature. We describe how the tactile system of the crayfish Cherax destructor functioned when subjected to the kind of damage found in wild-caught or cultured animals. Touch information was methodically varied by the removal of antennae and chelae. The resulting behaviour was analysed in a T-maze. Crayfish with a single antenna ablated turned toward the intact appendage, however, those with only a partial ablation did not, suggesting that a tactile information threshold exists for normal behaviour. When exposed to the same environment after an antennal ablation but with no prior experience in that terrain, crayfish also turned toward the side of the intact antenna. By contrast, when animals with experience obtained in a previous trial with intact antennae were tested after ablation of one antenna, they did not turn into one arm of the maze more than the other. These two outcomes indicate that behaviour is affected by an interaction between the time at which an injury occurs and an animal's knowledge of the topography, and that an injury may affect learning. We also tested to see if other appendages could provide tactile information to compensate for antennal loss. Input from the chelae did not affect the turning behaviour of crayfish in the maze.

Corners and bubble wrap: the structure and texture of surfaces influence crayfish exploratory behaviour.

Touch is a principal sense in all animals. It is potentially important in species of freshwater crayfish that encounter murky waters or are nocturnal. Little is known about how tactile (touch) stimuli affect exploratory behaviour under these conditions. We placed animals in different tactile situations at the start of an exploration in a dark arena and tracked the position of the body and antennae to test whether subsequent search behaviour was affected. Individuals were exposed to differently textured walls, channelled out along a wall, or released in contact with no, one, or two walls. A corner arrangement of surfaces, where individuals started near two walls at right angles, produced behaviour that differed from that of other configurations; animals chose one wall and then maintained a close distance from the wall along which they were moving. The distance from a wall adopted by a crayfish walking parallel to it was affected by the texture of the wall. These results on the influence of tactile stimuli on crayfish exploratory behaviour may have implications for other taxa.

Erectile dysfunction in spinal cord injury: a cost-utility analysis.

BACKGROUND: There is a high incidence of erectile dysfunction after spinal cord injury. This can have a profound effect on quality of life. Treatment options for erectile dysfunction include sildenafil, intracavernous injections of papaverine/alprostadil (Caverject), alprostadil/papaverine/phentolamine ("Triple Mix"), transurethral suppository (MUSE), surgically implanted prosthetic device and vacuum erection devices. However, physical impairments and accessibility may preclude patient self-utilization of non-oral treatments. METHODS: The costs and utilities of oral and non-oral erectile dysfunction treatments in a spinal cord injury population were examined in a cost-utility analysis conducted from a government payer perspective. Subjects with spinal cord injury (n=59) reported health preferences using the standard gamble technique. RESULTS: There was a higher health preference for oral therapy. The cost-effectiveness results indicated that sildenafil was the dominant economic strategy when compared with surgically implanted prosthetic devices, MUSE(R) and Caverject. The incremental cost-utility ratios comparing sildenafil with triple mix and vacuum erection devices favoured sildenafil, with ratios less than CAN$20,000 per quality adjusted life year gained. CONCLUSION: Based on this study, we conclude that sildenafil is a cost-effective treatment for erectile dysfunction in the spinal cord injury population.

The activity of abdominal stretch receptors during non-giant swimming in the crayfish Cherax destructor and their role in hydrodynamic efficiency.

Recordings were made from the nerve innervating the stretch receptors of the abdominal muscle receptor organs and slow extensor muscles of tethered crayfish, Cherax destructor, during so-called "non-giant swimming". The stretch receptors were active during the flexor phase of swimming but the duration and pattern of activity varied from cycle to cycle. Their pattern of firing was modified by the activity of the large accessory neurons which make direct inhibitory synapses upon them. Neither the stretch receptors nor the accessory neurons were active during the extensor phase of the cycle. The timing and extent of tailfan movements during the period of stretch receptor activity were measured from video records before and after the stretch receptor nerves were cut in the second to fifth segments. The promotion of the tailfan during flexion was significantly delayed and the minimum angle to which the uropods were remoted at the end of flexion significantly larger in denervated animals. We propose that afferent information from the stretch receptors coordinates the timing and extent of tailfan movements according to variations in the positioning and movement of the abdominal segments such that the hydrodynamic efficiency of the tailfan is enhanced on a cycle by cycle basis during non-giant swimming.

Two-pore domain K channel, TASK-1, in pulmonary artery smooth muscle cells.

Pulmonary vascular tone is strongly influenced by the resting membrane potential of smooth muscle cells, depolarization promoting Ca2+ influx, and contraction. The resting potential is determined largely by the activity of K+-selective ion channels, the molecular nature of which has been debated for some time. In this study, we provide strong evidence that the two-pore domain K+ channel, TASK-1, mediates a noninactivating, background K+ current (IKN), which sets the resting membrane potential in rabbit pulmonary artery smooth muscle cells (PASMCs). TASK-1 mRNA was found to be present in PASMCs, and the membranes of PASMCs contained TASK-1 protein. Both IKN and the resting potential were found to be exquisitely sensitive to extracellular pH, acidosis inhibiting the current and causing depolarization. Moreover, IKN and the resting potential were enhanced by halothane (1 mmol/L), inhibited by Zn2+ (100 to 200 micromol/L) and anandamide (10 micromol/L), but insensitive to cytoplasmic Ca2+. These properties are all diagnostic of TASK-1 channels and add to previously identified features of IKN that are shared with TASK-1, such as inhibition by hypoxia, low sensitivity to 4-aminopyridine and quinine and insensitivity to tetraethylammonium ions. It is therefore concluded that TASK-1 channels are major contributors to the resting potential in pulmonary artery smooth muscle. They are likely to play an important role in mediating pulmonary vascular responses to changes in extracellular pH, and they could be responsible for the modulatory effects of pH on hypoxic pulmonary vasoconstriction.

Sarcolemma agonist-induced interactions between InsP3 and ryanodine receptors in Ca2+ oscillations and waves in smooth muscle.

Smooth muscle cells respond to InsP(3)-generating (sarcolemma-acting) neurotransmitters and hormones by releasing Ca(2+) from the internal store. However, the release of Ca(2+) does not occur uniformly throughout the cytoplasm but often into a localized area before being transmitted to other regions of the cell in the form of Ca(2+) waves and oscillations to actively spread information within and between cells. Yet, despite their significance, our understanding of the generation of oscillations to waves is incomplete. A major aspect of controversy centres on whether or not Ca(2+) released from the InsP(3) receptor activates RyRs (ryanodine receptors) to generate further release by Ca(2+)-induced Ca(2+) release and propagate waves or whether the entire process arises from InsP(3) receptor activity alone. Under normal physiological conditions the [Ca(2+)] required to activate RyR (approx. 15 microM) exceeds the bulk average [Ca(2+)](c) (cytoplasmic Ca(2+) concentration) generated by InsP(3) receptor activity (<1 microM). Progression of waves and oscillations by RyR activity would require a loss of control of RyR activity and an unrestrained positive feedback on Ca(2+) release. Under store-overload conditions, RyR Ca(2+) sensitivity is increased and this enables waves to be induced by RyR activity. However, the relevance of these Ca(2+)-release events to normal physiological functioning is unclear. The InsP(3) receptor, on the other hand, is activated by Ca(2+) over the physiological range (up to 300 nM) and deactivated by higher [Ca(2+)](c) (>300 nM), features that favour intermittent activity of the receptor as occurs in waves and oscillations. Experimental evidence for the involvement of RyR relies mainly on pharmacological approaches in the intact cell where poor drug specificity could have led to ambiguous results. In this brief review the possible interactions between InsP(3) receptors and RyR in the generation of oscillations and waves will be discussed. Evidence is presented that RyRs are not required for InsP(3)-mediated Ca(2+) transients. Notwithstanding, ryanodine can inhibit InsP(3)-mediated Ca(2+) responses after RyR activity has been induced by caffeine or by steady depolarization which evokes spontaneous transient outward currents (a sarcolemmal manifestation of RyR activity). Ryanodine inhibits InsP(3)-mediated Ca(2+) transients by depleting the store of Ca(2+) rather than by RyR involvement in the InsP(3)-mediated Ca(2+) increase.

Parathyroid hormone-related protein (PTHrP) production sites in elasmobranchs.

This study describes the distribution of parathyroid hormone-related protein (PTHrP) antigen and its mRNA in seven species of cartilaginous fish from six elasmobranch families. Antigen was detected using antibodies to synthetic human PTHrP and the mRNA with a riboprobe to human PTHrP gene sequence. The distribution pattern of PTHrP in the cartilaginous fish studied, reflected that observed in mammals but PTHrP further occurs in some sites unique to cartilaginous fish. Of particular note was the demonstration of PTHrP in the shark skeleton, which although considered not to contain bone, may form by a process similar to that forming the early stages of mammalian endochondral bone. The distribution of PTHrP in the elasmobranch skeleton resembled the distribution of PTHrP in the developing mammalian skeleton. Differences in the staining pattern between antisera to N-terminal PTHrP and mid-molecule PTHrP in the brain and pituitary suggested that the PTHrP molecule might be post-translationally processed in these tissues. The successful use of antibodies and a probe to human PTHrP in tissues from the early vertebrates examined in this study suggests that the PTHrP molecule is conserved from elasmobranchs to humans.

The cord stretch receptors in the abdominal nerve cord of the crayfish Cherax destructor: physiology and relationships.

The physiology and relationships of tonic cord stretch receptor neurons in the crayfish Cherax destructor were examined with intracellular and extracellular recording. Cord stretch evoked slow depolarisations leading to action potentials in tonic cord stretch receptor neurons. Intermittent post-synaptic potentials were also seen in cord stretch receptor neurons but were not the primary cause of the action potentials. Cord stretch still evoked action potentials in cord stretch receptor neurons when all synaptic activity, monitored at another known chemical synapse, was blocked using high [Mg(2+)] and low [Ca(2+)] in the bath. One source of facilitating excitatory post-synaptic potentials in the cord stretch receptor neurons was from mechanosensory hairs on the dorsal abdominal surface. Tonic cord stretch receptor neuron activity was associated with an increase in the activity of the abdominal slow extensor inhibitor motor neuron and at least one abdominal flexor excitor motor neuron in its segment, and reduced activity in the abdominal slow flexor inhibitor motor neuron. Activation of individual cord stretch receptor neurons produced a local resistance reflex. Cord stretch, activating many receptors, produced several other outcomes. One was the "extensor state" described in earlier literature. The tonic cord stretch receptor neurons of Cherax destructor appear to be stretch-sensitive interneurons that receive inputs from other elements of the abdominal control system and mediate polysynaptic reflex activity in postural motor neurons.

Muscle receptor organs do not mediate load compensation during body roll and defense response extensions in the crayfish Cherax destructor.

It has been proposed that the abdominal muscle receptor organ (MRO) of decapod crustaceans acts in a sensory feedback loop to compensate for external load. There is not yet unequivocal evidence of MRO activity during slow abdominal extension in intact animals, however. This raises the possibility that MRO involvement in load compensation is context-dependent. We recorded from MRO tonic stretch receptors (SRs) in freely behaving crayfish (Cherax destructor) during abdominal extension occurring during two different behaviors: body roll and the defense response. Abdominal extensions are similar in many respects in both behaviors, although defense response extensions are more rapid. In both situations, SR activity typically ceased when the abdominal extension commenced, even if the joint of the SR being monitored was mechanically prevented from extending by a block. Since extensor motor neuron activity increased when the abdomen was prevented from extending, we concluded that the load compensation occurring in these behaviors was not mediated by the MROs.

Laboratory and field studies on the effect of molinate, clomazone, and thiobencarb on nontarget aquatic invertebrates.

The midge Chironomus tepperi was used in laboratory experiments to assess the relative toxicity of formulated molinate, clomazone, and thiobencarb, three herbicides used in Australian rice crops. Static bioassays were initiated with first-instar larvae at herbicide concentrations between 0.0625 and 2 times the anticipated field concentrations (AFCs) expected from the registered application rates. Adult emergence success, development time, and wing length were used as indices of the effect of each herbicide. Clomazone had no effect on any parameters at concentrations up to 0.288 mg/L (p > 0.05). Molinate significantly increased development time at concentrations equivalent to the AFC (3.6 mg/L) and above (p < 0.05). Thiobencarb reduced emergence success of adult C. tepperi at 0.0625 times the AFC (0.1875 mg/L) as well as decreasing male adult size and increasing development time for males and females at 0.125 times the AFC (p < 0.05). Nontarget effects of the herbicides on aquatic invertebrate communities were assessed in shallow experimental ponds using commercial application rates. One week after treatment, only thiobencarb had a significant effect, suppressing populations of chironomids, calanoids, and cyclopoids (p < 0.05). Four weeks later, all populations had recovered, equaling or exceeding control densities.

A general strategy for the synthesis of cladiellin diterpenes: enantioselective total syntheses of 6-acetoxycladiell-7(16),11-dien-3-ol (deacetoxyalcyonin acetate), cladiell-11-ene-3,6,7-triol, sclerophytin A, and the initially purported structure of sclerophytin A.

Enantioselective total syntheses of the cladiellin diterpenes, 6-acetoxycladiell-7(16),11-dien-3-ol (deacetoxyalcyonin acetate, 6), cladiell-11-ene-3,6,7-triol (1), sclerophytin A (8), and tetracyclic diether 7, have been achieved by differential elaboration of tricyclic allylic alcohol 57. The central step in these syntheses is acid-promoted condensation of alpha,beta-unsaturated aldehydes 45, 69 or 87, and cyclohexadienyl diol 44 to form, with complete stereocontrol, the hexahydroisobenzofuran core and five stereocenters of these cladiellin diterpenes. These syntheses also feature stereospecific photolytic deformylation of beta,gamma-unsaturated aldehydes 46, 70, and 71 to remove the extraneous carbon introduced in the Prins-pinacol step; chemo- and stereoselective hydroxyl-directed epoxidation of 49, 72, and 90 followed by regioselective reductive opening with hydride to install the C3 tertiary hydroxyl group; and a diastereoselective Nozaki-Hiyama-Kishi cyclization of iodoaldehyde 56 to forge the oxacyclononane ring and the C6 hydroxyl stereocenter. Other key transformations include chemo- and stereoselective hydroxyl-directed epoxidation of tricyclic allylic alcohol 57 followed by regioselective reductive opening with hydride to install the C7 tertiary hydroxyl center of 1 and 8; chemo-, regio-, and stereoselective intramolecular oxymercuration-reductive demercuration of dienyl diol 62 to form the bridging tetrahydropyran ring of tetracyclic diether 7; and photochemical isomerization of the endocyclic double bond of 92 and 1 to give exocyclic congeners 7 and 8. The absolute stereochemistry of the synthetic products originates from two chiral nonracemic starting materials, (S)-(+)-carvone and (S)-(-)-glycidol. These syntheses define a versatile and concise strategy for the total synthesis of cladiellin diterpenes and provide additional illustrations of the uncommon utility of pinacol-terminated cationic cyclizations for the stereocontrolled synthesis of complex oxacyclic products.