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The activation of O(2) at thiolate–ligated iron(ii) sites is essential to the function of numerous metalloenzymes and synthetic catalysts. Iron–thiolate bonds in the active sites of nonheme iron enzymes arise from either coordination of an endogenous cysteinate residue or binding of a deprotonated thiol-containing substrate. Examples of the latter include sulfoxide synthases, such as EgtB and OvoA, that utilize O(2) to catalyze tandem S─C bond formation and S-oxygenation steps in thiohistidine biosyntheses. We recently reported the preparation of two mononuclear nonheme iron–thiolate complexes (1 and 2) that serve as structural active-site models of substrate-bound EgtB and OvoA (Dalton Trans. 2020, 49, 17745–17757). These models feature monodentate thiolate ligands and tripodal N(4) ligands with mixed pyridyl/imidazolyl donors. Here, we describe the reactivity of 1 and 2 with O(2) at low temperatures to give metastable intermediates (3 and 4, respectively). Characterization with multiple spectroscopic techniques (UV-vis absorption, NMR, variable-field and -temperature Mössbauer, and resonance Raman) revealed that these intermediates are thiolate-ligated iron(iii) dimers with a bridging oxo ligand derived from the four-electron reduction of O(2). Structural models of 3 and 4 consistent with the experimental data were generated via density functional theory (DFT) calculations. The combined experimental and computational results illuminate the geometric and electronic origins of the unique spectral features of diiron(iii)-μ-oxo complexes with thiolate ligands, and the spectroscopic signatures of 3 and 4 are compared to those of closely-related diiron(iii)-μ-peroxo species. Collectively, these results will assist in the identification of intermediates that appear on the O(2) reaction landscapes of iron–thiolate species in both biological and synthetic environments.

Development of accurate disease models and discovery of immune-modulating drugs is challenged by the immune system’s highly interconnected and context-dependent nature. Here we apply deep-learning-driven analysis of cellular morphology to develop a scalable “phenomics” platform and demonstrate its ability to identify dose-dependent, high-dimensional relationships among and between immunomodulators, toxins, pathogens, genetic perturbations, and small and large molecules at scale. High-throughput screening on this platform demonstrates rapid identification and triage of hits for TGF-β- and TNF-α-driven phenotypes. We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. The presented library of images, deep learning features, and compound screening data from immune profiling and COVID-19 screens serves as a deep resource for immune biology and cellular-model drug discovery with immediate impact on the COVID-19 pandemic.

We have calculated the figure of equilibrium of a rapidly rotating, differentiated body to determine the shape, structure, and composition of the dwarf planet Haumea. Previous studies of Haumea's light curve have suggested that Haumea is a uniform triaxial ellipsoid consistent with a Jacobi ellipsoid with axes ≈960 × 774 × 513 km and bulk density ≈2600 kg m−3. In contrast, observations of a recent occultation of Haumea indicate that its axes are ≈1161 × 852 × 523 km and its bulk density is ≈1885 kg m−3; these results suggest that Haumea cannot be a fluid in hydrostatic equilibrium and must be supported by interparticle forces. We have written a code to reconcile these contradictory results and to determine whether Haumea is in fact a fluid in hydrostatic equilibrium. The code calculates the equilibrium shape, density, and ice crust thickness of a differentiated Haumea after imposing axis lengths a and b. We find that Haumea is consistent with a differentiated triaxial ellipsoid fluid in hydrostatic equilibrium with axes of best fit a = 1050 km, b = 840 km, and c = 537 km. This solution for Haumea has ρ avg = 2018 kg m−3, ρ core = 2680 kg m−3, and core axes a c = 883 km, b c = 723 km, and c c = 470 km, which equates to an ice mantle composing ~17% of Haumea's volume and ranging from 67 to 167 km in thickness. The thick ice crust we infer allows for Haumea's collisional family to represent only a small fraction of Haumea's pre-collisional ice crust. For a wide range of parameters, the core density we calculate for Haumea suggests that today the core is composed of hydrated silicates and likely underwent serpentinization in the past.

Background Semi-synthetic oleanane triterpenoid antioxidant inflammation modulators (tpAIMs) are small molecules that interact with KEAP1 cysteine residue 151 (C151) and activate NRF2. Exploration of the structure-activity relationship between the tpAIMs and KEAP1 is limited by the predominantly hydrocarbon nature of the oleanane triterpenoid pentacyclic ring structure. Therefore, we used novel, chemically-tractable, synthetic antioxidant inflammation modulators (sAIMs) to probe the stereoselectivity of the ligand-protein interaction. Methods We measured several parameters of NRF2 activation to assess the potency of sAIM enantiomers with natural (tpAIM-like) 4(S),5(S),10(R) or unnatural 4(R),5(R),10(S) configurations. Additionally, we determined the crystal structure of the KEAP1 BTB domain in complex with two different sAIMs. Results We found that the potencies of sAIM enantiomers in the natural configuration were similar to those of the tpAIM, RTA 405. Strikingly, sAIM enantiomers in the unnatural configuration were 10- to 40-fold less potent than their natural counterparts. Crystallographic studies of sAIMs in complex with the KEAP1 BTB domain demonstrated that these ligands form a covalent bond with C151 and revealed the presence of additional hydrogen bonds, Van der Waals interactions, and pi-stacking interactions. Conclusions Although KEAP1 C151 is required for NRF2 activation by tpAIMs and sAIMs, interactions with other KEAP1 residues are critical for the stereospecific recognition and potency of these ligands. General significance This work demonstrates that reversible cyanoenone Michael acceptors, such as the tpAIMs and sAIMs, can be specifically tuned to regulate redox sensitive cysteine residues on key signaling molecules, an approach with significant promise for innovative drug development.

Synthetic triterpenoids are antioxidant inflammation modulators (AIMs) that exhibit broad anticancer activity. AIMs bind to KEAP1 and inhibit its ability to promote NRF2 degradation. As a result, NRF2 increases transcription of genes that restore redox balance and reduce inflammation. AIMs inhibit tumor growth and metastasis by increasing NRF2 activity in the tumor microenvironment and by modulating the activity of oncogenic signaling pathways, including NF-κB, in tumor cells. Accumulating evidence suggests that KEAP1 loss or mutation--which results in high levels of sustained NRF2 activity--may promote cancer growth and increase chemoresistance. Loss of KEAP1 also increases the levels of other oncogenic proteins, including IKKβ and BCL2. The apparent survival advantage provided to some tumor cells by loss of functional KEAP1 raises the question of whether pharmacological inhibition of KEAP1 could promote tumor growth. To address this issue, we characterized the basal levels of KEAP1 and NRF2 in a panel of human tumor cell lines and profiled the activity of an AIM, RTA 405. We found that in tumor cell lines with low or mutant KEAP1, and in Keap1-/- murine embryonic fibroblasts, multiple KEAP1 targets including NRF2, IKKβ, and BCL2 were elevated. Keap1-/- murine embryonic fibroblasts also had higher rates of proliferation and colony formation than their wild-type counterparts. In cells with functional KEAP1, RTA 405 increased NRF2 levels, but not IKKβ or BCL2 levels, and did not increase cell proliferation or survival. Moreover, RTA 405 inhibited growth at similar concentrations in cells with different basal NRF2 activity levels and in cells with wild-type or mutant KRAS. Finally, pre-treatment with RTA 405 did not protect tumor cells from doxorubicin- or cisplatin-mediated growth inhibition. Collectively, these data demonstrate that pharmacological activation of NRF2 by AIMs is distinct from genetic activation and does not provide a growth or survival advantage to tumor cells.

The regulation of glycogen metabolism is critical for the maintenance of glucose and energy homeostasis in mammals. Glycogen synthase, the enzyme responsible for glycogen production, is regulated by multisite phosphorylation in yeast and mammals. We have previously identified PAS kinase as a physiological regulator of glycogen synthase in Saccharomyces cerevisiae . We provide evidence here that PAS kinase is an important regulator of mammalian glycogen synthase. Glycogen synthase is efficiently phosphorylated by PAS kinase in vitro at Ser-640, a known regulatory phosphosite. Efficient phosphorylation requires a region of PAS kinase outside the catalytic domain. This region appears to mediate a direct interaction between glycogen synthase and PAS kinase, thereby targeting kinase activity to this substrate specifically. This interaction is regulated by the PAS kinase PAS domain, raising the possibility that this interaction (and phosphorylation event) is modulated by the cellular metabolic state. This mode of regulation provides a mechanism for metabolic status to impinge directly on the cellular decision of whether to store or use available energy.

OBJECTIVE: To report the occurrence of lithium intoxication in a patient with bipolar disorder after adding rofecoxib to the medication regimen. CASE SUMMARY: A 68-year-old woman with bipolar disorder under long-term treatment with lithium, carbamazepine, pipamperon, and mirtazapine was prescribed rofecoxib 25 mg twice daily for the treatment of leg pain. Within one week, she showed progressive hypokinesia and tremor, which was treated with propranolol. Subsequently, she developed bradycardia, necessitating treatment with isoproterenol. Her lithium serum concentration had doubled compared with those before rofecoxib, and her renal function had deteriorated. After stopping lithium and rofecoxib, her laboratory values and neurologic signs improved or normalized within 2 days. An objective causality assessment revealed a probable relationship between concomitant use of the drugs and the resulting symptoms. DISCUSSION: As of May 24, 2004, only 3 cases of reversible lithium intoxication as a result of a possible interaction with rofecoxib or celecoxib have been previously reported. The mechanism of the interaction between lithium and cyclooxygenase (COX) 2 selective inhibitors is most probably related to inhibition of renal synthesis of prostaglandins, which are important for the maintenance of renal perfusion and tubular function. Impairment of renal blood flow, leading to a decrease in the glomerular filtration rate, and increased proximal tubular absorption are the most likely mechanisms by which COX-2 selective inhibitors reduce lithium clearance. CONCLUSIONS: Coadministration of rofecoxib and lithium may result in life-threatening lithium intoxication, especially in patients with a preexisting decrease in renal function and/or decreased intravascular volume.

The recent and forthcoming availability of high resolution satellite image series offers new opportunities in agro-hydrological research and modeling. We investigated the perspective offered by improving the crop growth dynamic simulation using the distributed agro-hydrological model, Topography based Nitrogen transfer and Transformation (TNT2), using LAI map series derived from 105 Formosat-2 (F2) images during the period 2006–2010. The TNT2 model (Beaujouan et al., 2002), calibrated with discharge and in-stream nitrate fluxes for the period 1985-2001, was tested on the 2006–2010 dataset (climate, land use, agricultural practices, discharge and nitrate fluxes at the outlet). A priori agricultural practices obtained from an extensive field survey such as seeding date, crop cultivar, and fertilizer amount were used as input variables. Continuous values of LAI as a function of cumulative daily temperature were obtained at the crop field level by fitting a double logistic equation against discrete satellite-derived LAI. Model predictions of LAI dynamics with a priori input parameters showed an temporal shift with observed LAI profiles irregularly distributed in space (between field crops) and time (between years). By re-setting seeding date at the crop field level, we proposed an optimization method to minimize efficiently this temporal shift and better fit the crop growth against the spatial observations as well as crop production. This optimization of simulated LAI has a negligible impact on water budget at the catchment scale (1 mm yr−1 in average) but a noticeable impact on in-stream nitrogen fluxes (around 12%) which is of interest considering nitrate stream contamination issues and TNT2 model objectives. This study demonstrates the contribution of forthcoming high spatial and temporal resolution products of Sentinel-2 satellite mission in improving agro-hydrological modeling by constraining the spatial representation of crop productivity.

The contribution of tropical coastal rivers to the global carbon budget remains unmeasured, despite their high water dynamics, i.e. higher run-off with their basin characteristic of warm temperature. Two rivers draining the western part of the Western Ghats, the Swarna (length 80 km) and Nethravati (147 km) Rivers, were studied for water and carbon cycles.The stable isotope ratios of oxygen (δ(18) O values), hydrogen (δ(2) H values) and carbon (δ(13) C values) were used to understand the water circulation, the weathering processes and the carbon biogeochemical cycle. The river water samples were collected during the dry post-monsoonal season (November 2011).The δ(18) O and δ(2) H values of river water suggested that the monsoonal vapour source and its high recycling have a dominant role because of the orographical and tropical conditions. The absence of calcareous rocks has led to dissolved inorganic carbon (DIC) mainly originating from atmospheric/soil CO2 , via rock-weathering processes, and the low soil organic matter combined with high run-off intensity has led to low riverine dissolved organic carbon (DOC) contents. The δ(13) C values increase from upstream to downstream and decrease with increasing pCO2 . There is a positive relationship between the δ(13) CDIC values and the DOC concentrations in these two rivers that is contrary to that in most of the studied rivers of the world.The higher evapotranspiration supported by tropical conditions suggests that there are higher vapour recycling process in the Swarna and Nethravati basins as studied from the water δ(18) O and δ(2) H values. The basin characteristics of higher rainfall/run-off accompanied by warm temperature suggest that the δ(13) C value of riverine DIC is mainly controlled by the weathering of source rocks (silicates) with variation along the river course by CO2 degassing from the river water to the atmosphere and is less dominated by the oxidation of DOC.

To compare the vertical distributions of benthos and fish species of Upper Lake Constance (Bodensee), 552 benthos samples were taken with an Auerbach grab at four transects (10–250 m). An additional 54 samples (1–10 m) were collected elsewhere. Complementary data was taken from the literature. In winter, most fish feed on benthos, mainly chironomids, but in summer less than 5% do so. Formerly the bottom gill-netting aimed mainly at catchingCoregonus pidschian, but it now aims atPerca fluviatilis. Contrary to expectation, in winter the greatest abundance ofP. fluviatilis is much deeper (55 m) than that of its preferred food, i.e. chironomids (

We describe a fully automated and autonomous air-borne biothreat detection system for biosurveillance applications. The system, including the nucleic-acid-based detection assay, was designed, built and shipped by Microfluidic Systems Inc (MFSI), a new subsidiary of PositiveID Corporation (PSID). Our findings demonstrate that the system and assay unequivocally identify pathogenic strains of Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia mallei, and Burkholderia pseudomallei. In order to assess the assay's ability to detect unknown samples, our team also challenged it against a series of blind samples provided by the Department of Homeland Security (DHS). These samples included natural occurring isolated strains, near-neighbor isolates, and environmental samples. Our results indicate that the multiplex assay was specific and produced no false positives when challenged with in house gDNA collections and DHS provided panels. Here we present another analytical tool for the rapid identification of nine Centers for Disease Control and Prevention category A and B biothreat organisms.

The isotopic signature of Dissolved Inorganic Carbon (DIC), δ(13)C(DIC), has been investigated in the surface waters of a small agricultural catchment on calcareous substratum, Montoussé, located at Auradé (south-west France). The Montoussé catchment is subjected to intense farming (wheat/sunflower rotation) and a moderated application of nitrogenous fertilizers. During the nitrification of the NH(4)(+), supplied by fertilization, nitrate and H(+) ions are produced in the soil. This anthropogenic acidity is combined with the natural acidity due to carbonic acid in weathering processes. From an isotopic point of view, with 'natural weathering', using carbonic acid, δ(13)C(DIC) is intermediate between the δ(13)C of soil CO(2) produced by organic matter oxidation and that of the carbonate rocks, while it has the same value as the carbonates when carbonic acid is substituted by another acid like nitric acid derived from nitrogen fertilizer. The δ(13)C(DIC) values range from -17.1‰ to -10.7‰ in Montoussé stream waters. We also measured the δ(13)C of calcareous molassic deposits (average -7.9‰) and of soil organic carbon (between -24.1‰ and -26‰) to identify the different sources of DIC and to estimate their contribution. The δ(13) C(DIC) value indicates that weathering largely follows the carbonic acid pathway at the springs (sources of the stream). At the outlet of the basin, H(+) ions, produced during the nitrification of N-fertilizer, also contribute to weathering, especially during flood events. This result is illustrated by the relationship between δ(13)C(DIC) and the molar ratio NO(3)(-)/(Ca(2+) + Mg(2+)). Consequently, when the contribution of nitrate increases, the δ(13)C(DIC) increases towards the calcareous end-member. This new isotopic result provides evidence for the direct influence of nitrogen fertilizer inputs on weathering, CO(2) consumption and base cation leaching and confirms previous results obtained using the chemistry of the major ions present in the field, and in soil column experiments.

Second mitochondria-derived activator of caspase (Smac) is a mitochondrial protein released into the cytosol during apoptosis. Smac mimetics have recently been touted as a novel therapeutic to induce apoptosis in cancer cells. The ability of Smac mimetics to induce apoptosis in vitro has been shown to be dependent upon both XIAP neutralization and cancer cell autocrine tumor necrosis factor-α (TNF-α) production. In this study we provide new evidence for the utility of Smac mimetics in combination with conventional chemotherapy agents to exacerbate caspase activation and induce cancer cell death. Furthermore, we find that the combination effect is because of a multifaceted mechanism involving both inhibition of cell proliferation by the chemotherapy agents and an enhanced autocrine TNF-α feedback loop by the Smac mimetic/chemotherapy agent combination. Surprisingly, although genotoxic agents typically induce apoptosis through the mitochondrial intrinsic pathway, we show that this synergism is mediated through a TNF-α/RIP1-dependent pathway, leading to activation of the extrinsic apoptotic pathway. Finally, we report that autocrine TNF-α contributes to Smac mimetic-induced tumor regression as a single agent or in combination with chemotherapeutics in xenograft mouse models. Collectively, we provide mechanistic and applicable data to support translational studies in the use of a Smac mimetic/chemotherapy antineoplasm modality.

The processes underlying development, refinement, and retention of the intracortical connections critical for the function of the mammalian brain are unknown. Horseradish peroxidase-labeled fibers in mouse somatosensory barrel cortex, which is patterned like the whiskers on the contralateral face from which it receives inputs, were evaluated by automated image analysis. The sensory nerve to the whiskers was sectioned on postnatal day 7, after the whisker map is set. The deprived barrel cortices, examined in adults, showed drastically diminished intracortical projections relative to normal controls, although the map of the whiskers in the cortex was unchanged. This demonstrates anatomically that the normal pattern of intracortical connections, like the normal sensory map, is dependent upon the sensory periphery four synapses away.

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Semi-synthetic triterpenoids are antioxidant inflammation modulator (AIM) compounds that inhibit tumor cell growth and metastasis. Compounds in the AIM class bind to Keap1 and attenuate Nrf2 degradation. In the nucleus, Nrf2 increases antioxidant gene expression and reduces pro-inflammatory gene expression. By increasing Nrf2 activity, AIMs reduce reactive oxygen species and inflammation in the tumor microenvironment, which reverses tumor-mediated immune evasion and inhibits tumor growth and metastasis. AIMs also directly inhibit tumor cell growth by modulating oncogenic signaling pathways, such as IKKβ/NF-κB. Here, we characterized the in vitro antioxidant, anti-inflammatory, and anticancer activities of RTA 408, a novel AIM that is currently being evaluated in patients with advanced malignancies. At low concentrations (≤ 25 nM), RTA 408 activated Nrf2 and suppressed nitric oxide and pro-inflammatory cytokine levels in interferon-γ-stimulated RAW 264.7 macrophage cells. At higher concentrations, RTA 408 inhibited tumor cell growth (GI50 = 260 ± 74 nM) and increased caspase activity in tumor cell lines, but not in normal primary human cells. Consistent with the direct effect of AIMs on IKKβ, RTA 408 inhibited NF-κB signaling and decreased cyclin D1 levels at the same concentrations that inhibited cell growth and induced apoptosis. RTA 408 also increased CDKN1A (p21) levels and JNK phosphorylation. The in vitro activity profile of RTA 408 is similar to that of bardoxolone methyl, which was well-tolerated by patients at doses that demonstrated target engagement. Taken together, these data support clinical evaluation of RTA 408 for cancer treatment.

Objectives: A set of standard processes was developed for delivering continuous drug infusions in order to improve (1) patient safety; (2) efficiency in staff workflow; (3) hemodynamic stability during infusion changes, and (4) efficient use of resources. Failure modes effects analysis (FMEA) was used to examine the impact of process changes on the reliability of delivering drug infusions. Setting: An 11 bed multidisciplinary pediatric ICU in the children's hospital of an academic medical center staffed by board certified pediatric intensivists. The hospital uses computerized physician order entry for all medication orders. Methods: A multidisciplinary team characterized key elements of the drug infusion process. The process was enhanced to increase overall reliability and the original and revised processes were compared using FMEA. Resource consumption was estimated by reviewing purchasing and pharmacy records for the calendar year after full implementation of the revised process. Staff satisfaction was evaluated using an anonymous questionnaire administered to staff nurses in the ICU and pediatric residents who had rotated through the ICU. Results: The original process was characterized by six elements: selecting the drug; selecting a dose; selecting an infusion rate; calculating and ordering the infusion; preparing the infusion; programming the infusion pump and delivering the infusion. The following practice changes were introduced: standardizing formulations for all infusions; developing database driven calculators; extending infusion hang times from 24 to 72 hours; changing from bedside preparation by nurses to pharmacy prepared or premanufactured solutions. FMEA showed that the last three elements of the original process had high risk priority numbers (RPNs) of >225 whereas the revised process had no elements with RPNs >100. The combined effect of prolonging infusion hang times, preparation in the pharmacy, and purchasing premanufactured solutions resulted in 1500 fewer infusions prepared by nurses per year. Nursing staff expressed a significant preference and pediatric residents unanimously expressed a strong preference for the revised process. Conclusions: Standardization of infusion delivery reduced the frequency for completing the most unreliable elements of the process and reduced the riskiness of the individual elements. Both contribute to a safer system.

An analysis of the computed tomograms of the paranasal sinuses from 200 patients with sinonasal complaints is presented. The results of our study are similar to those of other reported series despite a different patient selection. We have developed a simple systematic reporting scheme which includes all of the relevant abnormalities, and which allows a much more detailed picture of the disease pattern to be generated for both clinical use and for analytical studies.

The authors describe the surgery carried out for 11 carotid body tumours (CBTs) that were found in three generations of a Greek family. Eight patients with CBTs were operated upon at St. Joseph's Health Centre, Toronto, within 1 year. Three patients had bilateral CBTs, which were removed in two stages. Only one of the CBTs occurred in a female. Seven CBTs were excised by meticulous subadventitial dissection. In the eighth, a previous attempt at removal in another hospital had proved unsuccessful, and excision of the tumour required ligation of the external carotid artery and partial excision of the carotid bulb. The authors conclude that most CBTs can be excised directly without ligation, shunts or bypasses. In eight operations carried out on five patients, the only complication was a transient neuropraxia of the hypoglossal nerve that resolved within 2 weeks.

The ASA triad comprises bronchial asthma, acetylsalicylic acid (ASA) sensitivity and nasal polyps. It presents as chronic rhinitis followed by bronchial asthma and ASA sensitivity, and later nasal polyps. The pathogenesis of the ASA triad may involve interrelationships between disease in the upper and lower airway and hypersensitivity to cyclo-oxygenase inhibiting medications. Treatment of the nasal polyps has been shown to improve the patients' asthma.

Summary Bimetallic Ni-Mo catalysts promoted with potassium supported on manganese oxide or more particularly on zinc oxide are active and selective for the conversion of syngas into light alcohols. These alcohols could be via a CO insertion into a metal-alkyl bond or via an hydrofor-mylation type reaction. Indeed the rate of hydrocarbon and specially of alcohol formation are greatly enhanced by the addition of olefins.

With the growth of scientific knowledge in the health care disciplines, it has become increasingly difficult for practicing health care professionals to store and manipulate the information required to make clinical decisions. Where the decision making process can be defined and validated, expert systems will be able to assist beginning professionals to learn appropriate patterns of decision making. This article discusses the rationale for utilization of expert systems in a nursing environment. A prototype expert system called CAREPLAN, developed for use in an obstetrical environment, was built using Personal Consultant Plus, a software tool based on the LISP language. The project demonstrates that it is feasible to develop and validate an expert system for a specialized clinical environment in a relatively short period of time in comparison to traditional development methods. Graphics were used to enhance textual information and to increase user appeal. Strategies for future implementation and evaluation are outlined.

Blast tattoos occur when fragments of gunpowder are propelled into the skin during a firearm discharge. This unusual type of injury is often associated with accidents involving replica firearms. Some of the more superficially embedded powder fragments may be removed with dermabrasion; however, deeper fragments may cause permanent tattooing. Blast injuries to the face also have the potential of causing permanent eye injury.

A conceptual model of mime, as a therapeutic group activity, was dcsigned for this study. This model was based on May's (1958) description of three modes of world which characterize the existence of an individual. Eighteen chronic, adult psychiatric clients of a community-based day program met selection criteria for this study. Small mime groups were conducted by the researcher and pre- and post-testing was administered by the facility's staff occupational therapist. Assessment tools consisted of the human figure drawing, the Rosenberg Self-Esteem Scale and a movement-concept scale. Inter-rater reliability between the two raters ol the Goodenough rating scale were established for major body parts (.99, p S .05) and for body proportions (.93, p < .05). Results of matched pair t-tests (gain score analysis technique) indicated that only body-image as reflected by human figure'drawings in regard to proportionality was found to be significantly influenced by mime. Qualitative data related to structural and gra...

PAS kinase is a serine/threonine kinase regulated in cis by a PAS domain. A genetic study of the two PAS kinase genes in budding yeast gave evidence of the involvement of these enzymes in the control of sugar metabolism and translation. Using a biochemical screen for PAS kinase substrates, three translation factors were identified as direct phosphorylation targets. PAS kinase was also found to phosphorylate UDP-glucose pyrophosphorylase and glycogen synthase, the enzymes catalyzing the two final steps in the glycogen biosynthetic pathway. Genetic, biochemical, and physiological data provide evidence that both of these enzymes are inhibited by PAS kinase-dependent phosphorylation, thereby downregulating carbohydrate storage. These studies provide evidence of a cell-autonomous signaling system that both controls and connects the balance of fuel consumption/storage to protein synthesis.

Quantitation of oligosaccharide-bound galactose by galactose oxidase treatment of the higher sugar fraction is useful to screen honeys with normal stable carbon isotope ratio values for the presence of beet sugar products. For 23 beet sugar products tested, the mean bound galactose value was 30.1 mg/100 g (as galactose); for 81 honeys, the mean was 3.1 mg/100 g, s = 4.4. Nine percent of the honey samples tested had values in the beet sugar range, so additional testing by other procedures is required for confirmation of adulteration, i.e., samples with 8-80 mg/100 g bound galactose should be further tested.