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The few frontline antileishmanial drugs are poorly effective and toxic. To search for new drugs for this neglected tropical disease, we tested the activity of compounds in the Medicines for Malaria Venture (MMV) "Pathogen Box" against Leishmania amazonensis axenic amastigotes. Screening yielded six discovery antileishmanial compounds with EC50 values from 50 to 480 nM. Concentration-response assays demonstrated that the best hit, MMV676477, had mid-nanomolar cytocidal potency against intracellular Leishmania amastigotes, Trypanosoma brucei, and Plasmodium falciparum, suggesting broad antiparasitic activity. We explored structure-activity relationships (SAR) within a small group of MMV676477 analogs and observed a wide potency range (20-5000 nM) against axenic Leishmania amastigotes. Compared to MMV676477, our most potent analog, SW41, had ∼5-fold improved antileishmanial potency. Multiple lines of evidence suggest that MMV676477 selectively disrupts Leishmania tubulin dynamics. Morphological studies indicated that MMV676477 and analogs affected L. amazonensis during cell division. Differential centrifugation showed that MMV676477 promoted partitioning of cellular tubulin toward the polymeric form in parasites. Turbidity assays with purified Leishmania and porcine tubulin demonstrated that MMV676477 promoted leishmanial tubulin polymerization in a concentration-dependent manner. Analogs' antiparasitic activity correlated with their ability to facilitate purified Leishmania tubulin polymerization. Chemical cross-linking demonstrated binding of the MMV676477 scaffold to purified Leishmania tubulin, and competition studies established a correlation between binding and antileishmanial activity. Our studies demonstrate that MMV676477 is a potent antiparasitic compound that preferentially promotes Leishmania microtubule polymerization. Due to its selectivity for and broad-spectrum activity against multiple parasites, this scaffold shows promise for antiparasitic drug development.

Purpose: There is considerable interest in positive allosteric modulators (PAMs) of the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) subtype of ionotropic glutamate receptors as therapeutic agents for a range of cognitive and mood disorders. However, the challenge is to increase AMPA receptor (AMPAR) function sufficient to enhance cognitive function but not to the extent that there are mechanism-related pro-convulsant or convulsant side effects. In this present study, we report the preclinical pharmacology data for MDI-222, an AMPAR PAM which enhances cognition but has a much reduced side-effect (i.e. convulsant) liability relative to other molecules of this mechanism. Methods: The pharmacological effects of MDI-222 were characterised in in vitro and in vivo preclinical electrophysiology, efficacy (cognition), side-effect (pro-convulsant/convulsant), tolerability and toxicity assays. Results: We demonstrate that MDI-222 is an AMPAR PAM, since it enhanced AMPAR function in vitro at human (hGluA1-4) and rat (rGluA2) homomeric receptors, and potentiated hetero-oligomeric AMPARs in rat neurons. MDI-222 enhanced electrically evoked AMPAR-mediated synaptic transmission in the anaesthetised rat at 10 mg/kg (administered intravenously) and did not significantly lower the seizure threshold in the pro-convulsant maximal electroshock threshold test (MEST) at any dose tested up to a maximum of 30 mg/kg (administered by oral gavage (p.o.)). MDI-222 reversed a delay-induced deficit in novel object recognition (NOR) in rats with a minimum effective dose (MED) of 0.3 mg/kg (p.o.) following acute administration, which was reduced to 0.1 mg/kg following sub-chronic administration, and improved passive avoidance performance in scopolamine-impaired rats with a MED of 10 mg/kg p.o. On the other hand, MDI-222 was not pro-convulsant in the MEST, resulting in a therapeutic window between plasma concentrations that enhanced cognitive performance and those associated with mechanism-related side effects of ⩾1000-fold. Unfortunately, despite the excellent preclinical profile of this compound, further development had to be halted due to non-mechanism-related issues. Conclusions: We conclude that MDI-222 is an AMPAR PAM which enhances cognitive performance in rats and has a significantly improved safety profile in preclinical species.

Zoogloea oleivorans, capable of using toluene as a sole source of carbon and energy, was earlier found to be an active degrader under microaerobic conditions in aquifer samples. To uncover the genetic background of the ability of microaerobic toluene degradation in Z. oleivorans, the whole-genome sequence of the type strain BucT was revealed. Metatranscriptomic sequence reads, originated from a previous SIP study on microaerobic toluene degradation, were mapped on the genome. The genome (5.68 Mb) had a mean G + C content of 62.5%, 5005 protein coding gene sequences and 80 RNA genes. Annotation predicted that 66 genes were involved in the metabolism of aromatic compounds. Genome analysis revealed the presence of a cluster with genes coding for a multicomponent phenol-hydroxylase system and a complete catechol meta-cleavage pathway. Another cluster flanked by mobile-element protein coding genes coded a partial catechol meta-cleavage pathway including a subfamily I.2.C-type extradiol dioxygenase. Analysis of metatranscriptomic data of a microaerobic toluene-degrading enrichment, containing Z . oleivorans as an active-toluene degrader revealed that a toluene dioxygenase-like enzyme was responsible for the ring-hydroxylation, while enzymes of the partial catechol meta-cleavage pathway coding cluster were responsible for further degradation of the aromatic ring under microaerobic conditions. This further advances our understanding of aromatic hydrocarbon degradation between fully oxic and strictly anoxic conditions.

TIME is a mm-wavelength grating spectrometer array that will map fluctuations of the 157.7-μm emission line of singly ionized carbon ([CII]) during the epoch of reionization (redshift z ∼5–9). Sixty transition-edge sensor (TES) bolometers populate the output arc of each of the 32 spectrometers, for a total of 1920 detectors. Each bolometer consists of gold absorber on a ∼ 3 × 3 mm silicon nitride micro-mesh suspended near the corners by 1 × 1 × 500 μm silicon nitride legs targeting a photon-noise-dominated NEP ∼1×10^(-17)W/√Hz. Hafnium films are explored as a lower-T_c alternative to Ti (500 mK) for TIME TESs, allowing thicker support legs for improved yield. Hf T_c is shown to vary between 250 and 450 mK when varying the resident Ar pressure during deposition. Magnetic shielding designs and simulations are presented for the TIME first-stage SQUIDs. Total axial field suppression is predicted to be 5×10^7.

It is well known the dimerization state of receptor tyrosine kinases (RTKs), in conjunction with binding partners such as the growth factor receptor bound protein 7 (Grb7) protein, plays an important role in cell signaling regulation. Previously, we proposed, downstream of RTKs, that the phosphorylation state of Grb7SH2 domain tyrosine residues could control Grb7 dimerization, and dimerization may be an important regulatory step in Grb7 binding to RTKs. In this manner, additional dimerization-dependent regulation could occur downstream of the membrane-bound kinase in RTK-mediated signaling pathways. Extrapolation to the full-length (FL) Grb7 protein, and the ability to test this hypothesis further, has been hampered by the availability of large quantities of pure and stable FL protein. Here, we report the biophysical characterization of the FL Grb7 protein and also a mutant representing a tyrosine-phosphorylated Grb7 protein form. Through size exclusion chromatography and analytical ultracentrifugation, we show the phosphorylated-tyrosine-mimic Y492E-FL-Grb7 protein (Y492E-FL-Grb7) is essentially monomeric at expected physiological concentrations. It has been shown previously the wild-type FL Grb7(WT-FLGrb7) protein is dimeric with a dissociation constant (Kd) of approximately 11μM. Our studies here measure a FL protein dimerization Kd of WT-FL-Grb7 within one order of magnitude at approximately 1μM. The approximate size and shape of the WT-FL-Grb7 in comparison the tyrosine-phosphorylation mimic Y492E-FL-Grb7 protein was determined by dynamic light scattering methods. In vitro phosphorylation of the Grb7SH2 domain indicates only one of the available tyrosine residues is phosphorylated, suggesting the same phosphorylation pattern could be relevant in the FL protein. The biophysical characterization studies in total are interpreted with a view towards understanding the functionally active Grb7 protein conformation.

Oxygenic denitrification represents a new route in reductive nitrogen turnover which differs from canonical denitrification in how nitric oxide (NO) is transformed into dinitrogen gas. Instead of NO reduction via N2O to N2, NO is proposed to be directly disproportionated into N2 and O2 in oxygenic denitrification, catalyzed by the putative NO dismutase (Nod). Although a high diversity of nod genes has been recovered from various environments, still little is known about the niche partitioning and ecophysiology of oxygenic denitrifiers. One constraint is that nod as a functional marker for oxygenic denitrifiers is not well established. To address this issue, we compared the diversity and phylogeny of nod, 16S rRNA and pmoA gene sequences of four NC10 enrichments that are capable of methane-driven oxygenic denitrification and one environmental sample. The phylogenies of nod, 16S rRNA and pmoA genes of these cultures were generally congruent. The diversity of NC10 bacteria inferred from different genes was also similar in each sample. A new set of NC10-specific nod primers was developed and used in qPCR. The abundance of NC10 bacteria inferred from nod genes was constantly lower than via 16S rRNA genes, but the difference was within one order of magnitude. These results suggest that nod is a suitable molecular marker for studying the diversity and phylogeny of methane-driven oxygenic denitrifiers, the further investigation of which may be of value to develop enhanced strategies for sustainable nitrogen or methane removal.

SuperSpec is a novel on-chip spectrometer we are developing for multi-object, moderate resolution (R = 100 - 500), large bandwidth (~1.65:1) submillimeter and millimeter survey spectroscopy of high-redshift galaxies. The spectrometer employs a filter bank architecture, and consists of a series of half-wave resonators formed by lithographically-patterned superconducting transmission lines. The signal power admitted by each resonator is detected by a lumped element titanium nitride (TiN) kinetic inductance detector (KID) operating at 100 - 200 MHz. We have tested a new prototype device that achieves the targeted R = 100 resolving power, and has better detector sensitivity and optical efficiency than previous devices. We employ a new method for measuring photon noise using both coherent and thermal sources of radiation to cleanly separate the contributions of shot and wave noise. We report an upper limit to the detector NEP of $1.4\times10^{-17}$ W Hz$^{-1/2}$, within 10% of the photon noise limited NEP for a ground-based R=100 spectrometer., 8 pages, 4 embedded figures, accepted for publication in the Journal of Low Temperature Physics

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat552, increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat552 in the nucleus of inflamed and cancerous cells. Nuclear chromatin bound localization of LMW pβ-Cat552 was blocked in cells by inhibition of proteasomal chymotrypsin-like activity but not by other protease inhibitors. K48 polyubiquitinated FS and LMW β-catenin were increased by treatment with bortezomib. Overexpressed in vitro double truncated β-catenin increased transcriptional activity, cell proliferation and growth of tumor xenografts compared to FS β-catenin. Serine 552-> alanin substitution abrogated K48 polyubiquitination, β-catenin nuclear translocation and tumor xenograft growth. These data suggest that a novel proteasome-dependent posttranslational modification of β-catenin enhances transcriptional activation. Discovery of this pathway may be helpful in the development of diagnostic and therapeutic tools in colitis and cancer.

Microbial communities play key roles in remediation and reclamation of contaminated environments via biogeochemical cycling of organic and inorganic components. Understanding the trends in in situ microbial community abundance, metabolism and carbon sources is therefore a crucial component of effective site management. The focus of this study was to use radiocarbon analysis to elucidate the carbon sources driving microbial metabolism within the first pilot Wetland reclamation project in the Alberta oil sands region where the observation of H2S had indicated the occurrence of microbial sulphate reduction. The reclamation project involved construction of a three compartment system consisting of a freshwater wetland on top of a sand cap overlying a composite tailings (CT) deposit. Radiocarbon analysis demonstrated that both dissolved and sediment associated organic carbon associated with the deepest compartments (the CF and sand cap) was primarily fossil (Delta C-14 = -769 to -955 parts per thousand) while organic carbon in the overlying peat was hundreds to thousands of years old (Delta C-14 = -250 to -350 parts per thousand). Radiocarbon contents of sediment associated microbial phospholipid fatty acids (PLFA) were consistent with the sediment bulk organic carbon pools (Peat: Delta C-14(PLFA) = 257 parts per thousand; Sand cap Delta C-14(PLFA) = -805 parts per thousand) indicating that these microbes were using sediment associated carbon. In contrast, microbial PLFA grown on biofilm units installed in wells within the deepest compartments contained much more modern carbon that the associated bulk carbon pools. This implied that the transfer of relatively more modern carbon was stimulating the microbial community at depth within the system. Correlation between cellular abundance estimates based on PLFA concentrations and the Delta C-14(PLFA) indicated that the utilization of this more modern carbon was stimulating the microbial community at depth. These results highlight the importance of understanding the occurrence and potential outcomes of the introduction of relatively bioavailable carbon to mine wastes in order to predict and manage the performance of reclamation strategies.

We have built and tested 32-element linear arrays of absorber-coupled transition-edge sensors (TESs) read out with a time-division SQUID multiplexer. This detector/readout architecture is designed for the background-limited far-IR/submm spectrograph (BLISS) which is a broadband (35–433 $$\upmu $$ m), grating spectrometer consisting of six wavebands each with a modest resolution of R $$\sim $$ 700. Since BLISS requires the effective noise equivalent power (NEP) of the TESs to equal 1 $$\times $$ 10 $$^{-19}$$ W/Hz $$^{1/2}$$ , our detectors consist of very long (1–2 mm), narrow (0.4 $$\upmu $$ m), and thin (0.25 $$\upmu $$ m) Si $$_{x}$$ N $$_{y}$$ support beams that reduce the thermal conductance G between the substrate and the optical absorber. The thermistors of our lowest noise TESs consist of iridium with $$T_{c}=130$$ mK. We have measured the electrical properties of arrays of these Ir TESs with various meander and straight support beams and absorber shapes and found that G is $$\sim $$ 30 fW/K (meander) and $$\sim $$ 110 fW/K (straight), the electrical NEP is 2–3 $$\times $$ 10 $$^{-19}$$ W/Hz $$^{1/2}$$ (meander and straight), and the response time $$\tau $$ is 10–30 ms (meander) and 2–5 ms (straight). To reduce spurious or “dark” power from heating the arrays, we mounted the arrays into light-tight niobium boxes and added custom L/R and L/C low-pass chip filters into these boxes to intercept dark power from the bias and readout circuit. We found the average dark power equals 1.3 and 4.6 fW for the boxes with L/R and L/C chip filters, respectively. We have built arrays with $$T_{c}= 70$$ mK using molybdenum/copper bilayers and are working to lower the dark power by an order of magnitude so we can demonstrate NEP $$~=~1~\times $$ 10 $$^{-19}$$ W/Hz $$^{1/2}$$ with these arrays. PACS numbers: 85.25.Pb; 95.85.Gn; 95.85.Fm; 63.22. $$+$$ m

There are well validated rodent paradigms of schizophrenia which are based on environmental manipulation (e.g. altered rearing conditions) or drug challenges. These manipulations induce behavioural changes in rodents that are thought to involve neuronal circuitry similar to the ones that are affected by the pathophysiology of the disorder. This study has investigated whether three such rodent paradigms (isolation rearing, neonatal PCP treatment or sub-chronic PCP treatment) are associated with changes in muscarinic receptors (CHRMs) or ionotropic glutamate receptors, some of which have been reported to be altered in the CNS of subjects with schizophrenia. ( 3 H)pirenzepine (CHRM1), ( 3 H)4DAMP (CHRM1/CHRM3), ( 3 H)MK801 (NMDA receptors) and ( 3 H)kainate (kainate receptors; KAR) binding were measured using in situ radioligand binding and autoradiography. Isolation rearing caused widespread decreases in ( 3 H)4DAMP (p = 0.01) and ( 3 H)kainate binding (p = 0.03). Neonatal PCP caused widespread increases in ( 3 H)4DAMP binding (p

Multiple sclerosis is a chronic immune-mediated disease of the CNS. Although it is a predominantly T-cell mediated condition, B cells and autoreactive antibodies play an important role in its pathogenesis, with the presence of oligoclonal immunoglobulins in the cerebrospinal fluid being an important diagnostic indicator. The target of these immunoglobulins has not yet been fully characterized. However, post-translational modifications of CNS-specific proteins are thought to contribute to their production through the generation of novel epitopes. One post-translational modification in particular, the conversion of the amino acid arginine to the nonstandard amino acid, citrulline, has been increasingly described in the literature as a factor in the pathogenesis of this condition. In this article, we summarize and discuss the current knowledge on citrullination in multiple sclerosis, the importance of this in relation to its pathogenesis and, potentially, its diagnosis.

A series of N-substituted 3-(4-piperidinyl)-1,3-benzoxazolinones and oxindoles are reported which were found to be potent and selective muscarinic M 1 agonists. By control of the physicochemical characteristics of the series, particularly the lipophilicity, compounds with good metabolic stability and excellent brain penetration were identified. An exemplar of the series was shown to be pro-cognitive in the novel object recognition rat model of temporal induced memory deficit.

We evaluated locomotor hyperactivity induced in BALB/C mice by an N-methyl-D-aspartate receptor antagonist MK-801 as an assay for the detection of antipsychotic drugs.We assessed the effects of antipsychotic drugs to validate the assay (study 1), selective dopamine and serotonin ligands for pharmacological characterisation of the model (study 2) and a number of compounds with efficacy in models of schizophrenia to understand the predictive validity of the model (study 3).Adult males (n = 9/group) were pretreated with a test compound, habituated to locomotor activity cages before receiving MK-801 (0.32 mg/kg) and activity recorded for a further 75 or 120 min. In study 1, we tested haloperidol, clozapine, olanzapine, risperidone, ziprasidone, aripiprazole, sertindole and quetiapine. In study 2, we tested SCH23390 (D(1) antagonist), sulpiride (D(2)/D(3) antagonist), raclopride (D(2)/D(3) antagonist), SB-277011 (D(3) antagonist), L-745,870 (D(4) antagonist), WAY100635 (5-HT(1A) antagonist), 8-OH-DPAT (5-HT(1A) agonist), ketanserin (5-HT(2A)/5-HT(2C) antagonist) and SB-242084 (5-HT(2C) antagonist). In study 3, we tested xanomeline (M(1)/M(4) receptor agonist), LY379268 (mGluR2/3 receptor agonist), diazepam (GABA(A) modulator) and thioperamide (H(3) receptor antagonist).All antipsychotics suppressed MK-801-induced hyperactivity in a dose-dependent and specific manner. The effects of antipsychotics appear to be mediated via dopamine D(1), D(2) and 5-HT(2) receptors. Xanomeline, LY379268 and diazepam were active in this assay while thioperamide was not.MK-801-induced hyperactivity in BALB/C mice model of positive symptoms has shown predictive validity with novel compounds acing at M(1)/M(4), mGluR2/3 and GABA(A) receptors and can be used as a screening assay for detection of novel pharmacotherapies targeting those receptors.

Anion secretion by colonic epithelium is dependent on apical CFTR-mediated anion conductance and basolateral ion transport. In many tissues, the NKCC1 Na+-K+-2Cl−cotransporter mediates basolateral Cl−uptake. However, additional evidence suggests that the AE2 Cl−/HCO3−exchanger, when coupled with the NHE1 Na+/H+exchanger or a Na+-HCO3−cotransporter (NBC), contributes to HCO3−and/or Cl−uptake. To analyze the secretory functions of AE2 in proximal colon, short-circuit current ( Isc) responses to cAMP and inhibitors of basolateral anion transporters were measured in muscle-stripped wild-type (WT) and AE2-null (AE2−/−) proximal colon. In physiological Ringer, the magnitude of cAMP-stimulated Iscwas the same in WT and AE2−/−colon. However, the Iscresponse in AE2−/−colon exhibited increased sensitivity to the NKCC1 inhibitor bumetanide and decreased sensitivity to the distilbene derivative SITS (which inhibits AE2 and some NBCs), indicating that loss of AE2 results in a switch to increased NKCC1-supported anion secretion. Removal of HCO3−resulted in robust cAMP-stimulated Iscin both AE2−/−and WT colon that was largely mediated by NKCC1, whereas removal of Cl−resulted in sharply decreased cAMP-stimulated Iscin AE2−/−colon relative to WT controls. Inhibition of NHE1 had no effect on cAMP-stimulated Iscin AE2−/−colon but caused a switch to NKCC1-supported secretion in WT colon. Thus, in AE2−/−colon, Cl−secretion supported by basolateral NKCC1 is enhanced, whereas HCO3−secretion is diminished. These results show that AE2 is a component of the basolateral ion transport mechanisms that support anion secretion in the proximal colon.

Cadmium and other metallic ions can act as metalloestrogens and endocrine disruptors of reproductive tissues and fetal development in mammals, including humans. The detrimental effects occur with respect to the synthesis of both steroid and polypeptide hormones in the placenta. Leptin is produced by the trophoblast and may regulate fetal organogenesis and development. In human term placentas, concentrations of toxic metals and their effects on steroidogenesis were assessed in healthy parturients (109 non-smokers and 99 smokers) in relation to tobacco smoking. Trace elements (cadmium, lead, iron, zinc and copper) were analyzed in placentas using atomic absorption spectroscopy, and steroid hormones (progesterone and estradiol) were assayed in placental samples by an enzyme-immunometric method. Cadmium concentrations were doubled in placentas of smokers as compared with non-smokers, and placental lead and zinc concentrations increased significantly. Placental concentrations of iron, copper, progesterone and estradiol did not differ. In addition, human trophoblast cells were co-cultured with 0, 5, 10 or 20 microm CdCl(2) for 96 h and leptin mRNA assessed by quantitative polymerase chain reaction. Leptin mRNA declined dose-responsively as a result of CdCl(2) exposure. Collectively, the results confirm that human placental tissue offers a unique opportunity to biomonitor cadmium exposure in both the maternal and the internal fetal environments. In addition, the results strongly suggest that cadmium may cause a decline in placental leptin synthesis, as we have previously shown for placental progesterone production. This may constitute further evidence of the endocrine-disrupting effects of cadmium, as a constituent of tobacco smoke, on reproduction in women.

The development of novel anticonvulsant drugs with improved efficacy for the treatment of epilepsy is hindered by a lack of information regarding the quantitative relationship between target mechanism and in vivo efficacy. In the present study we have examined the correlation between the potency of structurally diverse compounds at voltage-gated sodium channels in vitro and their efficacy in a rodent model of acute generalised seizures induced by electroshock. We observed a significant correlation between the estimated affinity (Ki) of the compounds for the inactivated state of human recombinant Na(V)1.2 channels and the unbound brain concentration required for anticonvulsant efficacy. Furthermore, the data suggest that an unbound concentration equivalent to less than 50% of the Ki is sufficient for anticonvulsant effect. We noted that increasing sodium channel blocking potency was associated with increasing brain tissue binding and lipophilicity. These data suggest that there is a balance between sodium channel blocking potency in vitro and good pharmacokinetic characteristics necessary for anticonvulsant efficacy in vivo. Finally, we examined the sodium channel blocking potency of sodium valproate in relation to its anticonvulsant efficacy in vivo. We found that a higher unbound concentration of the drug in the brain was required for anticonvulsant efficacy than would be expected given its sodium channel blocking potency.

Chicken litter is often used in organic farming as a source of plant food, and to improve soil organic matter and microbial populations. Both positive and negative effects of such an amendment have been reported. Because of the complex interactions involving soil, plant, and microbial populations in the most common test systems, it is difficult to attribute the observed plant responses to any one component of the test system affected by chicken litter. We have therefore conducted studies on the chicken litter extracts in a soil-less system to ascertain whether chicken litter affects plants simply by providing plant nutrients or if it also affects plants through plant growth regulatory substances. Since chicken litter is generally rich in available ammonium nitrogen, we studied the effects of chicken litter extract on ammonium induced rise in putrescine levels in oat leaves. Our results showed increases in putrescine levels in oat leaves floating on ammonium sulfate solution (0.033%) but not in le...

様々な環境条件下での植物の応答や発育過程の制御にポリアミンが関与していることが知られている．オリーブではポリアミン含有量の季節変化や温度条件のポリアミン含有量への影響に関しては報告されているものの，栄養成長から生殖成長のような発育相の変化の過程にポリアミンがどのように関わっているのかはほとんど分かっていない．本研究では，着花誘導を行わない場合と低温処理などにより着花誘導を行って栄養成長から生殖成長に移行させた場合のオリーブ葉の遊離ポリアミン（プトレシン，スペルミジン，スペルミン）含有量の比較を行った．プトレシンとスペルミンは対照区である栄養成長を行っているオリーブの葉に比べて，低温処理により着花誘導を行った葉においては非常に高い含有量を示した．しかし，このようなポリアミンの増加は低温処理せずに着花誘導を行った樹では認められなかったことから，オリーブ葉での遊離型ポリアミン含有量の増加は発育相の変化によるものではなく，温度の影響によって引き起こされたものだと考えられた．このように遊離ポリアミン含有量はオリーブの生殖成長への相転換とは対応していないことが明らかとなった．一方，腋芽の遊離ポリアミン含有量は花芽へと発達するにともない増加したが，開花に至って減少した．花芽と比べて未熟果および成熟果におけるポリアミン含有量は少なかった．

Crop residue decomposition is affected by environmental factors and residue biochemical properties. These factors may contribute to management protocols that enhance soil organic matter accumulation in hot climates, which have characteristically high oxidation rates. The purpose of this experiment was to determine O 2 effects on soil polyphenol oxidase (PPO), peroxidase (PO), water-soluble polyphenolics (WEP), arginine ammonification (ARG), and water-extractable C (WEC). Cowpea (Vigna unguiculata L.) and sorghum [Sorghum bicolor (L.) Moench] residues in soil were incubated with headspace O 2 concentrations of 0.5, 10, or 21% (ambient) for up to 110 d. The PPO and PO were negatively related to WEP and WEC, mostly at 10 and 21% (P < 0.05). The WEP and WEC were significantly (P < 0.05) and negatively related to O 2 concentration. The WEP ranged from 0.5 mg kg -1 soil at 0.5% O 2 to near 0 at 10 and 21% O 2 . The WEC ranged from about 350 mg C kg -1 soil at 0.5% O 2 to

Trichloroethylene (TCE) in groundwater has the potential to volatilize through soil into indoor air where it can be inhaled. The purpose of this study was to determine whether individuals living above TCE-contaminated groundwater are exposed to TCE through vapor intrusion. We examined associations between TCE concentrations in various environmental media and TCE concentrations in residents. For this assessment, indoor air, outdoor air, soil gas, and tap water samples were collected in and around 36 randomly selected homes; blood samples were collected from 63 residents of these homes. Additionally, a completed exposure survey was collected from each participant. Environmental and blood samples were analyzed for TCE. Mixed model multiple linear regression analyses were performed to determine associations between TCE in residents' blood and TCE in indoor air, outdoor air, and soil gas. Blood TCE concentrations were above the limit of quantitation (LOQ; ≥ 0.012 µg L(-1)) in 17.5% of the blood samples. Of the 36 homes, 54.3%, 47.2%, and >84% had detectable concentrations of TCE in indoor air, outdoor air, and soil gas, respectively. Both indoor air and soil gas concentrations were statistically significantly positively associated with participants' blood concentrations (P = 0.0002 and P = 0.04, respectively). Geometric mean blood concentrations of residents from homes with indoor air concentrations of >1.6 µg m(-3) were approximately 50 times higher than geometric mean blood TCE concentrations in participants from homes with no detectable TCE in indoor air (P < .0001; 95% CI 10.4-236.4). This study confirms the occurrence of vapor intrusion and demonstrates the magnitude of exposure from vapor intrusion of TCE in a residential setting.

Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated β-catenin (pβ-Cat(Ser-552)) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85(ΔIEC)) mice develop more severe dextran sodium sulfate colitis due to delayed ulcer healing and reduced epithelial β-catenin activation. In colonic IEC, p85α deficiency did not alter PI3K signaling. In vitro shRNA depletion of individual complex members disrupts the MCC and reduces β-catenin signaling. Despite worse colitis, p85(ΔIEC) mice have reduced tumor burden after azoxymethane/dextran sodium sulfate treatment. Together the data indicate that the β-catenin MCC is needed for mucosal repair and carcinogenesis. This novel MCC may be an attractive therapeutic target in preventing cancer in colitis patients.

Previous studies suggest an interdependent relationship between liver and intestine for cholesterol elimination from the body. We hypothesized that a combination of ursodiol (Urso) and ezetimibe (EZ) could increase biliary secretion and reduce cholesterol reabsorption, respectively, to promote cholesterol excretion. Treatment with Urso increased hepatic ABCG5 ABCG8 (G5G8) protein and both biliary and fecal sterols in a dose-dependent manner. To determine whether the drug combination (Urso-EZ) further increased cholesterol excretion, mice were treated with Urso alone or in combination with two doses of EZ. EZ produced an additive and dose-dependent increase in fecal neutral sterol (FNS) elimination in the presence of Urso. Finally, we sequentially treated wide-type and G5G8-deficient mice with Urso and Urso-EZ to determine the extent to which these effects were G5G8 dependent. Although biliary and FNS were invariably lower in G5G8 KO mice, the relative increase in FNS following treatment with Urso alone or the Urso-EZ combination was not affected by genotype. In conclusion, Urso increases G5G8, biliary cholesterol secretion, and FNS and acts additively with EZ to promote fecal sterol excretion. However, the stimulatory effect of these agents was not G5G8 dependent.

Oleuropein is the most abundant biologically active phenolic compound in olives. It has been extensively studied for human health benefits but its role in plant development processes has received limited attention. Changes in the levels of oleuropein during early stages of flower formation and during fruit development and maturation were determined using high performance liquid chromatography. Oleuropein and other phenolic compounds were identified by comparing retention time and UV spectra with standard compounds using photodiode array detectors. Quantitative measurements were based on peak areas relative to standards. Oleuropein levels sharply decreased during the transition from vegetative to flower buds, consistent with earlier reports that higher levels of exogenously applied oleuropein inhibited flowering in Kalanchoe blossfeldiana. Oleuropein levels rapidly increased with the expansion of fertilized pistils and then sharply declined with fruit maturity. There was only a modest decline in oleuropein levels between immature and fully expanded leaves. Hesperidin, which occurs in relatively small amounts, also declined considerably during early floral buds formation. Maximum levels of verbascoside were found in fully developed green fruits while maximum levels of luteolin-7-O-glucoside and luteolin-4-O-glucoside were found in fully expanded leaves.

The purpose of this study was to investigate the uptake and elimination of perchlorate in eastern mosquitofish (Gambusia holbrooki). Fish were exposed to 0.1-1000 mg/l sodium perchlorate for 12h, 1, 2, 5, 10, and 30 days, and perchlorate was determined in whole body extracts. Perchlorate was not detected in mosquitofish exposed to the low concentrations of perchlorate (0, 0.1, and 1mg/l sodium perchlorate), regardless of the exposure time, whereas it was detected when fish were exposed to 10, 100, and 1000 mg/l. The tissue concentrations were approximately 10 times less than that in the water. There was no difference in the uptake of perchlorate depending upon the exposure time, however, a difference in perchlorate uptake depending upon the concentration of the exposure dose (P

The synthesis of new Pt3Tl complexes [Pt3{μ3-Tl(diketonate)(OH2)}(μ3-CO)(μ-dppm)3][PF6]2, 2, dppm = Ph2CH2PPh2, by reversible addition of thallium(I) β-diketonates to the complex cation [Pt3(μ3-CO)(μ-dppm)3]2+, is reported. The thallium(I) units are easily displaced from platinum by halide ions X− (X = Cl, Br, I) to give [Pt3(μ3-CO)(μ3-X)(μ-dppm)3]+, or by SnCl3− to give [Pt3(μ3-CO)(μ3-SnCl3)(μ-dppm)3]+. With trifluoroacetate there was an equilibrium with [Pt3(μ3-CO)(μ3-O2CCF3)(μ-dppm)3]+ and [Pt3{μ3-Tl(diketonate)(O2CCF3)}(μ3-CO)(μ-dppm)3]+. The structures of two Pt3Tl clusters are reported, and the Pt3Tl unit is shown to be tetrahedral.

The ability to evaluate individual HIV-1 virions from the quasispecies of vertically infected infants was evaluated in a field setting at the Centre for Infectious Disease Research in Zambia. Infant heel-prick blood specimens were spotted onto dried blood spot (DBS) filter paper cards at government health clinics. Nucleic acid was extracted and used as a template for HIV-1 proviral DNA detection by a commercial Amplicor HIV-1 PCR test (Roche, version 1.5). On samples that tested positive by commercial diagnostic assay, amplification of DNA was performed using an in-house assay of the 5′ and 3′ region of the HIV-1 genome. Additionally, fragments covering 1200 nucleotides within pol (full length protease and partial reverse transcriptase) and 1400 nucleotides within env (variable 1-variable 5 region) were further analyzed by single genome amplification (SGA). In summary, we have demonstrated an in-house assay for amplifying the 5′ and 3′ proviral HIV-1 DNA as well as pol and env proviral DNA fragments from DBS cards collected and analyzed entirely in Zambia. In conclusion, this study shows the feasibility of utilizing DBS cards to amplify the whole proviral HIV-1 genome as well as perform SGA on key HIV-1 genes.

Ocean colour data from the NASA Sea‐viewing Wide Field‐of‐view Sensor (SeaWiFS) was used to estimate chlorophyll a concentration around New Zealand on a monthly basis between September 1997 and May 2000. The performance of the SeaWiFS chlorophyll a algorithm (OC4v4) was investigated by comparing in situ measurements of the underwater light field with measurements of phytoplankton pigment concentration by High Performance Liquid Chromatography. The algorithm performed well for chlorophyll a concentrations below 0.6 mg m‐3 but overestimated by a factor of two or more at higher concentrations. The average chlorophyll a concentration for New Zealand Exclusive Economic Zone was calculated as an indication of the overall productivity of the region and varied between 0.26 and 0.43 mg m‐3 with no obvious relationship to the Southern Oscillation Index. New Zealand northern subtropical and Tasman Sea waters had a classical cycle of spring and autumn chlorophyll blooms consistent with production being co‐li...

Accuracy of the prediction of rill erodibility can be improved, in part, through an increased understanding of soil variables controlling particle detachment. To test the hypothesis that rill erodibility of clay-sand mixtures increases (i) as the dominant clay mineral changes from montmorillonite to illite to kaolinite, (ii) as total salt in the eroding fluid decreases, and (iii) when Ca is replaced by Na, concentrated flow erosion tests were conducted by mini-flume test procedures. Chelsea fine sand was mixed with 2 to 20% (w/w) Ca or Na forms of either kaolinite, illite, or montmorillonite, and water to a moisture potential of -490 Pa. Rill erodibility of Ca-montmorillonitesand mixtures was 4 to 40 times less than for Ca-illite-sand and Ca-kaolinite-sand mixtures. Na-montmorillonite-sand mixtures were one-half as erodible as Ca-montmorillonite, while Na-kaolinite and Na-illite were 3 to 25 times as erodible as their Ca forms. Decreasing salt concentration of the eroding fluid from 0.01 to 0.001 M in all cases decreased the critical shear stress value on average 0.8 Pa. Decreasing the salt concentration from 0.1 to 0.001 M had no effect on the erodibility of Ca-kaolinite and Na-montmorillonite, but increased the erodibility of Ca-illite and Ca-montmorillonite. The erodibility of clay-soil mixtures decreased from 9.6 to 0.04 ms m -1 as the water holding capacity of the clay in the mixture increased from 0.2 to 6.9 g g - and appears to be related to the effective surface area of the clay.

The biomass, composition, and grazing rates of three size fractions of mesozooplankton (200–500, 500–1000, and some >1000 μm) were estimated in shelf waters and the water masses associated with Subtropical Convergence east of New Zealand, in the austral winter and spring of 1993, as part of a larger New Zealand study of ocean carbon flux that contributes to the Joint Global Ocean Flux Study (JGOFS). The total biomass was largest in spring in all water types. It was similar to the biomass measurements made previously in subantarctic and subtropical water masses in the Southwest Pacific and those from the North Atlantic, except for the spring biomass in subtropical water which was unusually large (86.5 and 101.3 mg m-3 dry weight). Biomass was concentrated in the upper 100 m, especially within the 0–25 or 25–50 m layers, both day and night. Night/day biomass ratios in the surface 100 m were often >2, and are presumed to be the result of sampling patchy populations as well as vertical migration. Biomass was greatest for the >1000 μm fraction of the mesozooplankton population, followed by the 500–1000, and 200–500 μm fractions, respectively. The unusually small fraction of biomass residing in the 200–500 μm fraction is assumed to be the result of predation by larger mesozooplankton. The mesozooplankton community had maximum gut fluorescence at night only at stations where chlorophyll a was >2 mg m-3 and at many of the stations gut fluorescence was persistently low. This was probably the result of the poor feeding environment, since a large proportion of the primary production resided in the

The assimilation of nitrate (NO− 3), ammonium (NH+ 4), and urea by size‐fractionated natural assemblages of phytoplankton, as a function of the individual ambient nitrogen (N) nutrient concentrations, was investigated off the west coast of South Island, New Zealand, in February 1989. New production (ρ NO− 3) contributed by all three size classes was higher inshore than offshore, and accounted for 40–61% and 19–29% of the total N production (ZpN), respectively. The reverse was true for regenerated production [ρ NH+ 4 + ρurea], a clear indication of the importance of NH+ 4 and urea in offshore waters. Picoplankton (< 2 μm fraction), both inshore and offshore, was the major user of the regenerated N, and accounted for 43–62% of total regenerated production. The assimilation rates of all three size components achieved saturation at the larger additions of NO− 3, NH+ 4, and urea, and the half‐saturation constants (Ks) of all three N nutrients for the three size classes in summer were higher than the r...

The [M-H]- ions derived from tetrapeptides generally show two different collision-induced backbone cleavages which allow the determination of the amino acid sequence of the peptide. The first of these involves the formation of the carboxylate anions of either constituent amino acids or fragment peptides. In the second, amino acids or fragment peptides are eliminated as neutrals. There are a number of residues which undergo characteristic side-chain fragmentations irrespective of their position in the tetrapeptide, e.g. Ser, Thr, Cys, Met, Phe, and Tyr. However, there are also some residues which, when situated at the C-terminal end of the peptide, promote pronounced fragmentation at the C-terminal position which occurs to the exclusion of the normal backbone cleavages. We conclude that the data obtained from these negative-ion cleavages are analytically useful, and complement those provided by the cognate positive-ion technique.

We present new Herschel-SPIRE imaging spectroscopy (194-671 microns) of the bright starburst galaxy M82. Covering the CO ladder from J=4-3 to J=13-12, spectra were obtained at multiple positions for a fully sampled ~ 3 x 3 arcminute map, including a longer exposure at the central position. We present measurements of 12CO, 13CO, [CI], [NII], HCN, and HCO+ in emission, along with OH+, H2O+ and HF in absorption and H2O in both emission and absorption, with discussion. We use a radiative transfer code and Bayesian likelihood analysis to model the temperature, density, column density, and filling factor of multiple components of molecular gas traced by 12CO and 13CO, adding further evidence to the high-J lines tracing a much warmer (~ 500 K), less massive component than the low-J lines. The addition of 13CO (and [CI]) is new and indicates that [CI] may be tracing different gas than 12CO. No temperature/density gradients can be inferred from the map, indicating that the single-pointing spectrum is descriptive of the bulk properties of the galaxy. At such a high temperature, cooling is dominated by molecular hydrogen. Photon-dominated region (PDR) models require higher densities than those indicated by our Bayesian likelihood analysis in order to explain the high-J CO line ratios, though cosmic-ray enhanced PDR models can do a better job reproducing the emission at lower densities. Shocks and turbulent heating are likely required to explain the bright high-J emission., Accepted to The Astrophysical Journal. 17 pages + 20 pages of appendix figures

The mass spectra of (M - H)− ions derived from dipeptide methyl esters are not as useful from an analytical viewpoint as those of the underivatised peptides in that they lack the characteristic backbone cleavage which provides the primary sequencing data. Instead, major fragmentation occurs through the ester group, viz. competitive losses of MeOH and HCO2Me are noted. Specific fragmentations differentiate between dipeptide methyl esters containing C- and N-terminal Phe. Deuterium labelling and product ion studies have aided this investigation.

The reaction [Pt 3 (μ 3 -CO)(μ-dppm) 3 ] 2+ , 1, with RNC (R=A-Bu, cyclohexyl or o-xylyl) gives an intermediate characterized as [Pt 3 (μ-CO)(CNR)(μ-dppm) 3 ] 2+ , 2, which then isomerizes to the stable complex (Pt 3 (μ 3 -CO)-(CNR)(μ-dppm) 3 ] 2+ , 3. When R=o-xylyl, reaction of 3 with more RNC gives an intermediate [Pt 3 (μ-CO)-(CNR) 2 (μ-dppm) 3 ] 2+ , 4, which then loses CO to give (Pt 3 (CNR) 2 (μ-dppm)3] 2+ , 5, the first example of a Pt 3 cluster complex having no bridging atom

Bacterial regrowth potential in Southern California surface and groundwaters was evaluated for assimilable organic carbon (AOC) concentrations using two bioassays. Untreated and ozonated groundwaters were tested to determine variation in AOC with well site, season and static water depth. The mean total AOC concentration (Pseudomonas P17 + Spirillum NOX) for untreated groundwater was 54 μg carbon (C) l−1. Ozone treatment resulted in a 2 to 10-fold increase in AOC with an average concentration of 254 μg cl−1. Highly colored groundwaters (containing up to 250 platinum color units, pcu) were ozonated with 7 mg l−1 which was sufficient to remove up to 75 pcu of color but often resulted in AOC concentrations exceeding 500 μg Cl−1. In comparison, AOC levels in untreated surface waters were generally greater than 100 μg Cl−1 and showed less of an increase after ozonation than did groundwaters. Total organic carbon (TOC) concentrations ranged from 0.2 to 5.7 mg l−1 and most groundwater samples contained less than 1 mg l−1 TOC. There was no correlation between AOC and chemical parameters such as DOC, color or u.v. absorbance (254 nm). Ratios of AOC to DOC ranged from 0.5 to 31% which suggests that the majority of the organic carbon in groundwater and surface waters is biologically stable. In summary, AOC levels appeared to vary with well location and possibly with season. Therefore, routine monitoring of source and treated water must be conducted on a site specific basis to determine bacterial regrowth potential or biofilm formation. Appropriate treatment strategies can then be developed, on an area by area basis, to remove or reduce AOC levels.

A method for the purification of mouse monoclonal antibodies from hybridoma culture supernatants is described. The protocol involves the use of a combination of three previously described methods for the concentration and purification of monoclonal antibodies. Firstly, hybridomas were grown in a Diacult dialysis system (Inter Med Laboratory, Denmark) to yield milligram quantities of monoclonal antibody in a culture supernatant. Monoclonal antibodies were then purified from the culture supernatant by precipitation with polyethylene glycol 6000 (PEG 6000) and finally reprecipitated using an ammonium sulphate procedure. The PEG 6000 treatment caused a density change in the ammonium sulphate immunoglobulin precipitate, and resulted in the formation of a pellicle which contained pure mouse monoclonal antibody. The protocol removed contaminating bovine serum immunoglobulin as well as other serum and cellular protein from the monoclonal antibody preparations.

Glycine can act as either an inhibitory neurotransmitter or as a potentiator of NMDA-dependent excitatory neurotransmission. There is some evidence that glycine can have both pro- and anticonvulsant properties in various rodent models of epilepsy. In the present study we tested several glycine transporter 1 (GlyT1) inhibitors including NFPS, SSR 504734, Lu AA21279, Org 25935, SB-710622, GSK931145, as well as the glycine agonist d -serine, in the maximal electroshock threshold (MEST) test in the rat. In a series of experiments, male Sprague–Dawley rats (n = 12/group) were pre-treated with a compound of interest and then received an electric shock delivered via corneal electrodes. A cohort of satellite animals (n = 3/group) was also used to measure blood and brain levels of Org 25935. All GlyT1 inhibitors increased seizure thresholds dose-dependently, indicative of anticonvulsant activity. SB-710622 and GSK931145 had lower minimum effective doses (MEDs) in the MEST test than other GlyT1 inhibitors. At estimated tmax, increases in dose administered were paralleled by increases in blood and brain concentrations of Org 25935. Thus, increasing extracellular concentration of glycine via inhibition of its uptake protects from electroshock-induced seizures in the rat. Whether strychnine-sensitive or strychnine-insensitive glycine binding sites are involved in this effect remains to be determined.

The surface distribution of salinity, temperature, nitrate‐nitrogen (N03‐N), and chlorophyll a in the southern New Zealand, Foveaux Strait region in February 1977, 1978, 1979, and 1980 was highly variable. The source of new nitrogen appears to be incursions of high‐salinity water west and east of Stewart Island. Although it seems likely that the source of this high‐nutrient, high‐salinity water is vertical, a horizontal advective source cannot be ruled out The chlorophyll a content of surface waters was not related directly to the NO3‐N concentrations. This lower food chain variability may be linked to variability in economically important species. Oysters grew twice as fast in the summer of 1978/79 as they did in 1979/80. But the mean chlorophyll a values were very similar for February of both years (2.5 and 2.2 μg 1−1, respectively). The elevated NO3‐N levels in 1979 may have resulted in much higher phytoplankton levels later that summer and resulted in the higher oyster growth rate that year. ...

Organic matter is known to influence soil credibility, but little work has been done to determine the effects of specific organics on erosional processes. Our study was designed to assess the influence of organic polymers known to increase aggregate stability on nearsurface soil shear strength and soil detachment by single raindrops during time. An index of shear strength was obtained with a Swedish fall-cone device and detachment was based on soil loss in the splash of a single raindrop. Two soils with similar texture but differing organic-matter contents were used. Amendments studied were polyvinyl alcohol (PVA), an experimental starch graft polymer (SCP), and a mixture of a microbial polysaccharide rich in levans and other cellular material (LEV). The amendments initially induced significant increases in soil shear strength ranging from 1.5 to S.5 times greater than untreated soil. The pattern of change of shear strength during time was nearly identical for all treatments, and was attributed to an aging process. Significant changes induced by the amendments in the amount of soil detached varied with time. The patterns of change during time seen in the PVA-amended soils were similar to the controls, while the LEV and SCP response curves differed. In conjunction with decomposition-rate data, it was concluded that the transformation products formed during the decomposition of the LEV and SCP were causing temporal changes in the soil that the Swedish fall-cone device was insensitive to, but influenced the response of the soil to raindrop detachment. T EXTENT to which a soil erodes depends on the ability of soil structural units to withstand the forces of raindrop impact and surface flow (Meyer, 1981). Soil properties are known to affect a soil's susceptibility to erosion (Wischmeier and Mannering, 1969). Still, no single property has correlated closely to soil loss due to erosion, which caused Wischmeier and Mannering (1969) to use a multiple regression analysis technique to relate several soil properties to erosional losses. Properties contributing significantly to soil-loss variance are soil texture, organic-matter content, measurements of soil structure including aggregate stability, parent material, and residual effects of crops P.V. Barry and R.F. Turco, Dep. of Agronomy, Purdue Univ., West Lafayette, IN 47907; and D.E. Stott and J.M. Bradford, USDA-ARS National Soil Erosion Research Lab., Purdue Univ., West Lafayette, IN 47907. Joint contribution of the National Soil Erosion Research Lab., USDA-ARS and the Indiana Agric. Exp. Stn. Purdue Journal no. 117070. Received 12 Jan. 1990. 'Corresponding author. Published in Soil Sci. Soc. Am. J. 55:799-804 (1991). and management practices. Current erosion models are separating the erosion process into two components, rill and interrill erosion (Foster, 1987). For intertill credibility, the process of detachment due to raindrop impact predominates (Young and Wiersma, 1973). Soil properties shown to specifically affect soil detachment include organic-matter content (Young and Onstad, 1978), aggregate stability (Young and Onstad, 1978; Luk, 1979; Meyer and Harmon, 1984), and infiltration rates (Poesen and Savat, 1981). Soil shear strength has been used to predict soil erodibility or other soil-related processes (Foster, 1987). A field study by Watson and Laflen (1986) shows a close relation between interrill erosion and soil shear strength after rainfall. Current efforts to develop erosion-prediction models that are more process based than the older predictive technologies include measurements of soil-strength indices (Foster, 1987; Elliot et al., 1989). Cruse and Larson (1977) showed that soil shear strength measured by triaxial compression is related to soil detachment by single-raindrop impact. Al-Durrah and Bradford (1981) related shear strength as measured by the Swedish fall-cone device to detachment by raindrop from a soil in an uncrusted condition. Bradford et al. (1986) showed that, if a raindrop's kinetic energy is known, splash from a single raindrop on finer textured soils can be accurately predicted from shear strength derived from fall-cone measurements without having to correct for a soil's friction angle. None of these studies included time or aerobic incubation as factors. Many studies have been done on the relation between organic matter and soil structure. Organic matter stabilizes soil structure by binding particles into durable aggregates, forming an organo-mineral complex (Martin, 1971; Hayes, 1980; Tisdall and Oades, 1982). The resistance of an organo-mineral complex to microbial degradation determines the complex's duration and effectiveness in stabilizing soil particles (Martin, 1971; Olness and Clapp, 1972). Portions of the soil organic matter are in chemical forms that are resistant to microbial decomposition and remain in soil for many years; however, other components, such Abbreviations: LEV, bacterial polysaccharide rich in levans; PVA, polyvinyl alcohol; SGP, starch graft polymer; T, near-surface shear strength; 8, soil detachment due to single raindrops; LSI, least significant interval. 800 SOIL SCI. SOC. AM. J., VOL. 55, MAY-JUNE 1991 as microbial and root exopolysaccharides, may last only days to months in soil (Martin, 1971; Tisdall and Oades, 1982; Stott and Martin, 1990). Polysaccharides that are long, flexible, and have charged side groups are most effective in binding soil particles together (Martin, 1971; Hayes, 1980). While most of the work on relating soil erodibility to soil properties has dealt with total organic matter, little work has been done on the relation between specific types of organics present in the soil and changes in erodibility. Cruse and Larson (1977) added PVA to soil, then measured changes in soil strength and detachment due to raindrop impact. The PVA increased soil shear strength and decreased soil detachment with increasing concentrations, but the amendments were not allowed to undergo microbial transformation within the soil before testing. The first objective of this study was to determine if different types of polysaccharides added to soil would influence soil detachment by single raindrops and near-surface soil shear strength in a similar manner. We used three organic polymers known to increase aggregate stability, PVA, SGP, and LEV. Polyvinyl alcohol, a soil polysaccharide analog, has been, and still is, used as an amendment to improve soil structure. Starch graft polymer, also a soil polysaccharide analog, is being developed as a soil stabilizer (Weaver and Fanta, 1987; Weaver, 1988). The SGP is synthesized by grafting charged side chains of polymethyl acrylate to a cationic corn starch backbone (Weaver and Fanta, 1987). The LEV, a polysaccharide produced by a common soil microorganism, is probably produced within the soil environment and could be expected to undergo profound transformations before becoming part of the natural soil humus (Stott and Martin, 1990). A second objective was to determine if the initial changes seen would be sustained during time within a given soil type when allowed to incubate under aerobic conditions. Another objective was to determine if the linear relationship between soil detachment by single raindrop and soil shear strength as measured by the fall-cone device shown by Al-Durrah and Bradford (1981) would be maintained during time in the presence of decomposing organic amendments. MATERIALS AND METHODS

Une etude pilot a ete elaboree, en vue d'evaluer l'effet de l'ozonation sur la qualite de l'eau du Colorado qui alimente l'usine de traitement de Phoenix Union Hills par l'intermediaire du Canal «Central Arizona». Les principaux parametres de qualite chimiques et bacteriologiques ― y compris la totalite des coliformes ― ont ete saisis de maniere automatique dans l'eau brute et traitee. Conformement aux previsions, on constata un accroissement jusqu'a 1 ou 2 log du nombre de germes heterotrophes dans l'effluent des filtres, en absence d'une desinfection secondaire. L'elimination des bacteries heterotrophes atteignit 98,8% apres traitement combine d'ozone et de chlore, 94,5% apres ozonation et application de chloramine, et 85% seulement a l'aide d'une chloration

The complex [Pt 3 (μ 3 -CO)(μ-dppm) 3 ] 2+ (1; dppm-Ph 2 PCH 2 PPh 2 ) adds phosphorus donors L to give the adducts [Pt 3 (μ 3 -CO)(μ-dppm) 3 L] 2+ , where L=P(OMe) 3 , P(OEt) 3 , P(OPh) 3 , PMe 2 Ph, PMePh 2 , PPh 3 , PF 3

Several studies suggest that MutaMouse is insensitive to clastogens, including the accompanying paper by Mahabir et al., which describes a study with bleomycin, camptothecin, m-AMSA (4'-(9-acridinylamino)-methanesulfon-m-anisidide) and its ortho-analogue, o-AMSA (4'-(9-acridinylamino)-methanesulfon-o-anisidide). Only camptothecin was clastogenic in MutaMouse and none of these four compounds induced mutations at the lacZ locus. However, to improve exposure, dose range-finding studies were performed in CD2F1 mice, the parental strain of MutaMouse. Male CD2F1 mice (n=3) were treated with bleomycin (25-100 mg/kg bw, p.o. and i.p.), camptothecin (1-10 mg/kg bw p.o.) and m-AMSA (10-50mg/kg bw p.o. and 1-5 mg/kg bw i.p.) for 5 days and blood was sampled on day 3 and/or day 6 for analysis by flow cytometry to determine % MN-RETs. Camptothecin (1 mg/kg bw, day 6) induced a 3.6-fold increase in % MN-RET (P

The aggregation of cell surface FcRs by immune complexes induces a number of important Ab-dependent effector functions. However, despite numerous studies that examine receptor function, very little is known about the molecular organization of these receptors within the cell. In this study, protein complementation, mutagenesis, and ligand binding analyses demonstrate that human FcγRIIa is present as a noncovalent dimer form. Protein complementation studies found that FcγRIIa molecules are closely associated. Mutagenesis of the dimer interface, as identified by crystallographic analyses, did not affect ligand binding yet caused significant alteration to the magnitude and kinetics of receptor phosphorylation. The data suggest that the ligand binding and the dimer interface are distinct regions within the receptor, and noncovalent dimerization of FcγRIIa may be an essential feature of the FcγRIIa signaling cascade.

The purpose of this study was to determine the effects of perchlorate on thyroid function in mosquitofish. Adult mosquitofish were exposed to 0, 0.1, 1, 10, 100, and 1000 mg/L sodium perchlorate for 2, 10, and 30 d. Whole body thyroxin (T4) content and histological assessment of thyroid follicles (e.g., follicular epithelial height, hyperplasia, hypertrophy, and colloid depletion) were used to gauge alterations in thyroid function. Follicular epithelial cell height, hyperplasia, and hypertrophy increased with increasing perchlorate concentration, especially in fish exposed for 30 d, and these effects were statistically significantly different from control at concentrations as low as 0.1 mg/L (nominal concentration). The percent occurrence of follicles with depleted colloid decreased with increasing perchlorate concentration, which is contrary to what is expected with thyroid inhibition. There also was a decrease in whole body T4 concentration in fish exposed to perchlorate for 30 d, but clear dose-response relationships were less evident for whole body T4 than for histopathological endpoints. In conclusion, thyroid histopathology provides a sensitive biomarker for thyroid endocrine disruption at environmentally relevant concentrations of sodium perchlorate, and whole body T4 is a less sensitive indicator of perchlorate exposure than is histopathology.