Search

Fe-Cu oxides nanoparticles (Nps) were embedded in two steel slag wastes (SSB and SSW) to develop SSB/Fe-Cu and SSW/Fe-Cu nanocomposites. Nps with mean sizes between 10–20 and 6–10 nm on SSW and SSB, respectively are agglomeration with a different shape. Their characteristics were investigated by XRD, TEM, BET, SEM techniques. The Nps modified the morphology of both support materials. XRD pointed out the presence of Cu and Fe. The proportion of Cu concentration was higher than the one of Fe. Nanocomposites were tested in malachite green removal from aqueous solution. The adsorption kinetic indicated physisorption and chemisorption as the main mechanisms of adsorption. The adsorption capacities were 88.26 and 63.55 mg/g for SSW/Fe-Cu and SSB/Fe-Cu, respectively. This novel, easy to prepare and low-cost nanocomposites is an efficient adsorbent material. The presence of calcium compounds may improve Nps deposition an MG removal. Materials with ferric phases are not as efficient as the first one; Fe is not well supported on the material. The removal of MG took place by dye structure modification and by interactions with Cu nanoparticles improving the oxidation-reduction process, through synergic effects.

The essential oil (EO) from different genotypes of Lippia gracilis Schauer (Verbenaceae) present two distinctive chemotypes containing either thymol or its isomer carvacrol as major compounds, both of which have proven bioactivity against several agricultural pests. Recently, we have shown that L. gracilis accession LGRA 106 and its major compound thymol are toxic and repellent against the coconut mite, Aceria guerreronis Keifer (Acari: Eriophyidae), a key pest of coconut plantations in Asia, Africa and America. Since intraspecific variation affects the chemical composition of EO and hence, its bioactivity, here we assessed the acaricidal and repellent effects of L. gracilis accession LGRA109 to A. guerreronis. Leaves of this accession contain carvacrol (49.35%) as major compound. The LC50 of the EO and of carvacrol estimated for A. guerreronis were 28.01 and 6.84 mg/mL, respectively. Carvacrol, at its LC50, as well as the EO and carvacrol at their LC99, repelled the mite. Our results indicated that carvacrol and the EO of L. gracilis accession LGRA109 were bioactive against A. guerreronis; however, the EO was less effective than its major compound. Made available in DSpace on 2021-12-06T19:01:03Z (GMT). No. of bitstreams: 1 Teodoro-et-al2021-IJA.pdf: 644832 bytes, checksum: 90fd69cfc371be37e5ff9361d37b0a2b (MD5) Previous issue date: 2021

Complement Factor H-Related 3 (FHR-3) is a major regulator of the complement system, which is associated with different diseases, such as age-related macular degeneration (AMD). However, the non-canonical local, cellular functions of FHR-3 remained poorly understood. Here, we report that FHR-3 bound to oxidative stress epitopes and competed with FH for interaction. Furthermore, FHR-3 was internalized by viable RPE cells and modulated time-dependently complement component (C3, FB) and receptor (C3aR, CR3) expression of human RPE cells. Independently of any external blood-derived proteins, complement activation products were detected. Anaphylatoxin C3a was visualized in treated cells and showed a translocation from the cytoplasm to the cell membrane after FHR-3 exposure. Subsequently, FHR-3 induced a RPE cell dependent pro-inflammatory microenvironment. Inflammasome NLRP3 activation and pro-inflammatory cytokine secretion of IL-1ß, IL-18, IL-6 and TNF-α were induced after FHR-3-RPE interaction. Our previously published monoclonal anti-FHR-3 antibody, which was chimerized to reduce immunogenicity, RETC-2-ximab, ameliorated the effect of FHR-3 on ARPE-19 cells. Our studies suggest FHR-3 as an exogenous trigger molecule for the RPE cell “complosome” and as a putative target for a therapeutic approach for associated degenerative diseases.

Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer., In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

The role of land use and the physical environment in N and P pollution of alluvial aquifers was analysed at three levels of information: (1) aquifer (N and P in groundwater), (2) soil transect (potentially leachable N and P in the soil solution) and (3) aquifer's catchment area. The study was carried out in the Oja and Tirón alluvial aquifers and their catchment areas (northern Spain). Nitrate was the dominant N form, both in groundwater and the soil solution of aquifers’ catchment areas. Orthophosphate and organic–P were the codominant P forms in the aquifers. Orthophosphate was the main form in the soil solution. During the period 2005–2017 no significant decrease in nitrate pollution was observed, suggesting the need to review current Nitrate Vulnerable Zone (NVZ) designations. Since nitrate is highly mobile, it tended to accumulate in stagnation zones at the lower reaches of the aquifers. P did not accumulate in the same zones due to its low solubility. Principal component analyses (PCAs) of the aquifers, soil transects and aquifers’ catchment areas revealed that the observation scale influences the environmental factors that can be detected as intervening in groundwater pollution. At the aquifer scale, links were found between nitrates and land use, topographic, hydrogeological and climatic factors. The protective effect of natural areas against nitrate pollution was noteworthy, while agriculture was associated with pollution. At the soil transect scale, an altitudinal gradient governed soil particle size distribution and land use, separating mountain forest soils from agricultural soils. The negative relationship between clay contents vs. nitrate and orthophosphate in the soil solution pointed to a regulatory role of clay. At the catchment scale, the size and physical characteristics of the catchments and land use distribution determined macronutrient availability in the soil solution and, in turn, N and P groundwater distribution., The authors acknowledge the Spanish State Research Agency and the European Regional Development Fund for their financial support of Project CGL2016–81110–R (AEI/FEDER, UE).

Adsorption of commercial xanthate derivatives on copper sulfide mineral (covellite, CuS) was studied by kinetics and isotherm adsorption experiments. The adsorption of xanthate derivatives was confirmed by FTIR (Fourier transform infrared spectroscopy) and XPS (X-ray photoelectron spectroscopy) results. Experiments were performed with two different xanthate derivatives, C-4410 (O-pentyl S-2-propenyl ester) and C-4940 (isobutyl xanthogen ethyl formate), on individual doses of 0.05 g of powdered covellite. It was found that the equilibrium times at pH 2, 4, and 6 were different for both xanthate derivatives. The shortest times were achieved at pH 2 and 4. The results suggest that C-4110 can be used as collector in a wide range of pH, while C-4940 is limited to lower pH values. Pseudo first- and pseudo second-order kinetics models were thus applied to the experimental data for pH 2. The information obtained from the kinetics models combined with XPS allowed proposing the adsorption mechanism for the covellite-xanthate derivative pair. The adsorption takes place through a non-covalent interaction for C-4410 and chemisorption process for C-4940. The best-fitting isotherm models for C-4410 and C-4940 adsorption were Redlich–Peterson and Freundlich, respectively, which yield a maximum adsorption capacity of 57.07 mg g−1 for C-4410 and 44.62 mg g−1 for C-4940.

Upon damage by herbivores, plants induce an array of volatile organic compounds (VOCs) that mediate ecological interactions involving communication with organisms of the second and third trophic levels. VOC-mediated tritrophic interactions have largely been studied in various systems, including cassava (Manihot esculenta), but little is known about the chemical nature of herbivore-induced VOCs in this crop and the response they evoke in natural enemies. Several tetranychid and predatory mites are associated with cassava. Here, VOC emissions from uninfested plants and plants infested with 200 or 400 Mononychellus tanajoa, a specialist herbivore on cassava, and the generalists Tetranychus urticae and T. gloveri were measured. Dual-choice experiments were also conducted to assess the preference of inexperienced (reared on prey-infested bean plants) and experienced (adapted on prey-infested cassava plants) predatory mites, Neoseiulus idaeus (Phytoseiidae), between odors of uninfested plants versus odors of plants infested with M. tanajoa, T. urticae or T. gloveri. Two hundred individuals significantly increased the emissions of (Z)-3-hexen-1-ol, (E)-β-ocimene, β-caryophyllene, alloaromadendrene and (E)-geranyl acetone in T. urticae-infested plants, and (E)-β-ocimene and methyl salicylate (MeSA) in T. gloveri-infested plants. Four hundred individuals significantly increased the emissions of (Z)-3-hexen-1-ol, MeSA, α-pinene and D-limonene in M. tanajoa-infested plants. In addition, T. urticae at this density induced (E)-β-ocimene, D-limonene, (E)-geranyl acetone and six compounds that were not detected in other treatments. Tetranychus gloveri-infested plants induced the emissions of (E)-2-hexenal and D-limonene. Regardless of the infesting species, inexperienced N. idaeus did not discriminate between uninfested or infested plants. Upon experience, they discriminated between the odors of uninfested and T. urticae-damaged plants. Our findings reveal that mite infestations in cassava result in density-dependent and species-specific emission of VOCs, and that N. idaeus relies on associative learning to forage for its prey.

In the present work, 3-phenyl-1-propanol is proposed as a new collector for coal flotation in a low-rank carbonaceous mineral containing 2.0% of carbon and basic groups predominantly on the surface. Hydroxyl and carbonyl groups, as well as unsaturated carbon chains, were identified by FT-IR. Microflotation tests were conducted to evaluate and compare the effectiveness of the collector proposed with the one obtained using kerosene, diesel and 1-butylamine. Results show that the highest coal recovery is obtained with 3-phenyl-1-propanol. Mineral has a negative zeta potential in the pH range 2–13, but it does not show an isoelectric point. Furthermore, the zeta potential is modified by the collector. After conditioning, signals corresponding to the collector were identified in the mineral surface by FT-IR. A Box-Behnken experimental design was used for optimization of mineral Recovery and Clean Coal Recovery by flotation. Results showed that pH has not a significant effect on the mineral Recovery, however flotation time and volume of 3-phenyl-1-propanol have a significant direct effect. Optimal conditions for mineral Recovery were pH 8.5 and 84.5 µL of collector for 0.5 g of mineral. For Clean Coal Recovery; pH, flotation time and volume of 3-phenyl-1-propanol have a significant effect. Optimal conditions were pH 4.0, flotation time 2.5 min and 87.9 µL of collector for 0.5 g of mineral.

Widespread exposure to environmental endocrine disrupting chemicals (EDC) has been attributed in part to the rise in non-communicable diseases. Pregnant women and their developing fetuses are vulnerable to exposure from EDC leading to adult onset disorders in the offspring in accordance with the developmental origin of health and disease (DOHAD) hypothesis. Bisphenol A (BPA) is one such EDC with estrogenic, anti-androgenic, and metabolism disrupting properties. BPA has been detected in >90% of US population. Gestational BPA exposure has been found to be associated with low birth weight, a risk factor for adult onset diseases in both human and sheep. The low birth weight may be the consequence of reduced placental efficiency stemming from disruption in inflammatory, oxidative stress and metabolic homeostasis, such as that reported in pregnancies accompanying maternal obesity and gestational diabetes. We hypothesized that gestational BPA treatment at environmentally relevant levels leads to placental inflammation, oxidative stress and lipid accumulation during early pregnancy accounting for the poor birth outcome observed. Gestational day 65 placentae were collected from pregnant Suffolk treated with 0.5mg/kg/day BPA sc starting from day 30 of gestation. Controls received equal volume of corn oil (vehicle).This BPA dose produces 1.6 ng/mL BPA concentration in the umbilical artery, levels close to that observed in the maternal circulation in US. Inflammatory markers and antioxidant expression were determined by real time RT-PCR, byproducts of lipid peroxidation (index of oxidative damage) measured using thiobarbituric acid reactive substances (TBARS) assay, and lipid accumulation as an index of lipotoxicity by oil red O staining. Data were analyzed by Student’s t-test and Cohen’s effect size analysis. Prenatal BPA treatment induced a significant (p < 0.05) increase in antioxidants glutathione reductase, and superoxide dismutase 1 and 2. While Cohen’s effect size analysis showed (1) large magnitude increase in macrophage marker CD68 and medium magnitude increase in proinflammatory cytokines chemokine ligand 2 and interleukin 1 beta; (2) large magnitude increase in TBARS, and (3) medium magnitude increase in oil red O staining in placenta from prenatal BPA. These preliminary findings indicate that gestational BPA exposure induces early disruptions in placental milieu via increased inflammation, oxidative stress and lipid accumulation. The increase in antioxidant expression evidenced in placentae of prenatal BPA treated sheep may reflect a compensatory response to overcome the oxidative stress state. The altered placental milieu may lead to reduced placental efficiency thus contributing to the low birth weight and the cardio-metabolic defects seen in prenatal BPA-treated sheep. Supported by NIH ES-016541.

Transgenic soybean plants (RR) engineered to express resistance to glyphosate harbor a variant of the enzyme EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) involved in the shikimic acid pathway, the biosynthetic route of three aromatic amino acids: phenylalanine, tyrosine, and tryptophan. The insertion of the variant enzyme CP4 EPSPS confers resistance to glyphosate. During the process of genetic engineering, unintended secondary effects are likely to occur. In the present study, we quantified volatile organic compounds (VOCs) emitted constitutively or induced in response to herbivory by the soybean looper Chrysodeixis includens in transgenic soybean and its isogenic (untransformed) line. Since herbivore-induced plant volatiles (HIPVs) are known to play a role in the recruitment of natural enemies, we assessed whether changes in VOC profiles alter the foraging behavior of the generalist endoparasitic larval parasitoid, Meteorus rubens in the transgenic line. Additionally, we assessed whether there was a difference in plant quality by measuring the weight gain of the soybean looper. In response to herbivory, several VOCs were induced in both the conventional and the transgenic line; however, larger quantities of a few compounds were emitted by transgenic plants. Meteorus rubens females were able to discriminate between the odors of undamaged and C. includens-damaged plants in both lines, but preferred the odors emitted by herbivore-damaged transgenic plants over those emitted by herbivore-damaged conventional soybean plants. No differences were observed in the weight gain of the soybean looper. Our results suggest that VOC-mediated tritrophic interactions in this model system are not negatively affected. However, as the preference of the wasps shifted towards damaged transgenic plants, the results also suggest that genetic modification affects that tritrophic interactions in multiple ways in this model system.

Herbivory induces the emission of volatile organic compounds (VOCs) which are involved in the attraction of predators and parasitoids. In spite of the large number of studies that have addressed the electrophysiological and behavioral responses of natural enemies to herbivore-induced VOCs, whether herbivores perceive these compounds remains largely unknown. By coupling chemical and electrophysiological (Gas Chromatography–Mass Spectrometry GC–MS and Gas Chromatography–Electroantennography GC–EAG) techniques we identified individual compounds emitted by maize upon feeding by Spodoptera frugiperda Walker (Lepidoptera: Noctuidae) that elicit a response in conspecific females. Herbivory induced significantly the emission of β-myrcene, ( Z )-3-hexenyl acetate, ( E )-β-ocimene, β-linalool, ( E )-4,8-dimethyl-1,3,7-nonatriene [DMNT], indole, geranyl acetate, α-zingiberene, β-caryophyllene, ( E )-α-bergamotene, ( E )-β-farnesene, β-sesquiphellandrene, ( E )-nerolidol, and 4,8,12-trimethyl-1,3,7,11-tridecatetraene [TMTT]. From these, eleven compounds elicited a response in the antennae of S. frugiperda females (virgin and mated). The antennae of virgin and mated females responded consistently to ( Z )-3-hexenyl acetate, β-linalool, indole, ( E )-β-farnesene and TMTT. In addition the sesquiterpenes ylangene/(+)-cycloisosativene evoked a response in the antennae even though these compounds were not significantly increased upon herbivory. The numbers of antennae of virgin or mated females responding to individual compounds were similar even though a higher percentage of the antennae of gravid female tested responded to geranyl acetate. The results show that S. frugiperda detects several herbivore-induced VOCs emitted by maize plants. These compounds may be responsible for repellence previously observed in this species by volatiles induced by conspecifics.

Under acidic conditions, isobutyl xanthogen ethyl formate was used as a collector compound in the flotation process for Cu recovery from the mineral bornite (Cu5FeS4). The mineral sample was characterized by X-Ray Diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM) and X-Ray Photoelectron Spectroscopy (XPS) techniques. Also found in lower proportions were chalcopyrite and quartz. The bornite presented a rough and porous surface. The adsorption study included kinetics, thermodynamics, and isotherm tests. The equilibrium time at pH 2 was 15 min. The kinetics model suggest the adsorption can be described by two processes, both related to the formation of a chelate. Thermodynamically, the collector adsorption process is favored at room temperature, whereas the process is not favored at lower temperatures. The adsorption capacity was 8.8 mg g−1 achieved by a combination of mechanisms on a heterogeneous surface. Under local optimized conditions, the highest Cu recovery (96.98 %) was determined from an experimental design for an initial collector concentration of 20 mg L−1, a flotation time of 3 min, and pH = 2. Contact time of the collector with the mineral surface represents one of the most important variables in the flotation process. In addition, the combinations between pH-tf, Ci-tf, and pH-Ci-tf variables have the most significant effect on Cu recovery percentage. The collector can be used satisfactorily at lower pH values. Although the xanthogen formate functional group acted on both the Fe and Cu ions in the mineral, it was observed that the collector has a higher affinity for Cu ions compared with Fe ions.

Plants express inducible direct and indirect defenses in response to herbivory. The plant hormone jasmonic acid (JA) and related signaling compounds referred to as jasmonates play a central role in regulating defense responses to a wide range of herbivores.We assessed whether treating tomato seeds with 0.8 mM of methyl jasmonate (MeJA) affected the performance of the leaf miner Tuta absoluta, and whether possible changes in volatile profiles altered the behavior of its predator Chrysoperla externa. MeJA-treatment significantly lengthened larval development and decreased the pupal weight of T. absoluta. Herbivory alone increased the emissions of α-pinene, 6-methyl 5-hepten-2-one, β-myrcene, (E)-β-ocimene, isoterpinolene, TMTT, (Z)-3-hexenyl butyrate, and hexyl salicylate. MeJA seed treatment significantly decreased the emissions of α-cubebene from undamaged and herbivore-infested plants. In addition, the emissions of several compounds were lower in the absence of herbivory. Chrysoperla. externa preferred odors from herbivore-infested plants over those from control plants, regardless of the MeJA-treatment, and they did not show any preference for herbivore-infested plants for any of the MeJA-treatments. Our results show preliminary evidence that the treatment of tomato seeds with MeJA can reduce the performance of Tuta absoluta, and that the chemical differences observed in plant VOC profiles do not alter the behavior of the model predator.

To describe the subunit composition of glutamate and gamma-aminobutyric acid (GABA) receptors in brain tissue from patients with different types of status epilepticus.The subunit composition of glutamate and GABA receptors was analyzed in: (1) surgical brain samples from three patients with refractory convulsive status epilepticus, three patients with electrical status epilepticus in sleep, and six patients with refractory epilepsy, and (2) brain autopsy samples from four controls who died without neurological disorders. Subunit expression was quantified with Western blotting and messenger ribonucleic acid (mRNA) expression was quantified with reverse polymerase chain reaction.Western blot analysis demonstrated the following patterns (as compared to controls): (1) alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors: elevated GluA1/GluA2 ratio in electrical status epilepticus in sleep (465%±119) and refractory epilepsy (329%±125; p0.01); (2) N-methyl-d-aspartate (NMDA) receptors: increased GluN2B/GluN2A ratio in electrical status epilepticus in sleep (3682%±1000) and refractory convulsive status epilepticus (3520%±751; p0.05); (3) GABA receptors: elevated α2/α1 ratio in refractory epilepsy (321%±138; p0.05) and refractory convulsive status epilepticus (346%±74; p0.05); and (4) patients with underlying malformation of cortical development had increased ratios in GluA1/GluA2 (382%±149; p0.01), GluN2B/GluN2A (3321%±1581; p0.05) and α2/α1 (303%±86; p0.01). Quantification of mRNA demonstrated an elevated GABRA2/GABRA1 ratio in refractory epilepsy (712; p0.05) as compared to controls.The subunit composition of glutamate and GABA receptors in patients with status epilepticus mirrors that found in animal models of refractory status epilepticus and may promote self-sustaining seizures. Receptor subunit changes may provide additional targets for improved treatment.

In this work the influence of aqueous sulfur passivation on the surface of n-type (100) GaSb single crystals has been studied through low-temperature photoluminescence (PL) characterization. The samples were passivated at different times using aqueous solutions of sodium sulfide. PL spectroscopy was used to determinate the optimum time of sulfur passivation, through the measurement of the PL intensity for the different passivation times. For the samples measured, the PL spectra show the presence of two emission bands, whose intensity and energy position change for the different passivation times of the GaSb samples. According to the PL results, a passivation surface treatment of 6 min shows the highest PL intensity spectrum.

Summary This multicentre observational study evaluated the feasibility, efficacy and toxicity of antifungal combination therapy (combo) as treatment of proven or probable invasive fungal diseases (IFDs) in patients with haematological malignancies. Between January 2005 and January 2010, 84 cases of IFDs (39 proven and 45 probable) treated with combo were collected in 20 Hematological Italian Centres, in patients who underwent chemotherapy or allogeneic haematopoietic stem cell transplantation for haematological diseases. Median age of patients was 34 years (range 1–73) and 37% had less than 18 years. Acute leukaemia was the most common underlying haematological disease (68/84; 81%). The phase of treatment was as follows: first induction in 21/84 (25%), consolidation phase in 18/84 (21%) and reinduction/salvage in 45/84 (54%). The main site of infection was lung with or without other sites. The principal fungal pathogens were as follows: Aspergillus sp. 68 cases (81%), Candida sp. six cases (8%), Zygomycetes four cases (5%) and Fusarium sp. four cases (5%). The most used combo was caspofungin+voriconazole 35/84 (42%), caspofungin + liposomal amphotericin B (L-AmB) 20/84 (24%) and L-AmB+voriconazole 15/84 (18%). The median duration of combo was 19 days (range 3–180). The overall response rate (ORR) was 73% (61/84 responders) without significant differences between the combo regimens. The most important factor that significantly influenced the response was granulocyte (PMN) recovery (P 0.009). Only one patient discontinued therapy (voriconazole-related neurotoxicity) and 22% experienced mild and reversible adverse events (hypokalaemia, ALT/AST increase and creatinine increase). The IFDs-attributable mortality was 17%. This study indicates that combo was both well tolerated and effective in haematological patients. The most used combo regimens were caspofungin + voriconazole (ORR 80%) and caspofungin + L-AmB (ORR 70%). The ORR was 73% and the mortality IFD related was 17%. PMN recovery during combo predicts a favourable outcome. Clinical Trials Registration: NCT00906633.

The diagnosis of Parkinson's disease rests on motor signs of advanced central dopamine deficiency. There is an urgent need for disease biomarkers. Clinicopathological evidence suggests that α-synuclein aggregation, the pathological signature of Parkinson's disease, can be detected in gastrointestinal tract neurons in Parkinson's disease. We studied whether we could demonstrate α-synuclein pathology in specimens from unprepped flexible sigmoidoscopy of the distal sigmoid colon in early subjects with Parkinson's disease. We also looked for 3-nitrotyrosine, a marker of oxidative stress. Ten subjects with early Parkinson's disease not treated with dopaminergic agents (7 men; median age, 58.5 years; median disease duration, 1.5 years) underwent unprepped flexible sigmoidoscopy with biopsy of the distal sigmoid colon. Immunohistochemistry studies for α-synuclein and 3-nitrotyrosine were performed on biopsy specimens and control specimens from a tissue repository (23 healthy subjects and 23 subjects with inflammatory bowel disease). Nine of 10 Parkinson's disease samples were adequate for study. All showed staining for α-synuclein in nerve fibers in colonic submucosa. No control sample showed this pattern. A few showed light α-synuclein staining in round cells. 3-Nitrotyrosine staining was seen in 87% of Parkinson's disease cases but was not specific for Parkinson's disease. This study suggests a pattern of α-synuclein staining in Parkinson's disease that was distinct from healthy subjects and those with inflammatory bowel disease. The absence of this pattern in subjects with inflammatory bowel disease suggests it is not a sequel of inflammation or oxidative stress. 3-Nitrotyrosine immunostaining was common in all groups studied, suggesting oxidative stress in the colonic submucosa.

This review describes the effects of the current and emerging lighting technologies on plants, and the plant-mediated effects on herbivorous and beneficial arthropods in high-technology year-round greenhouse production, where light quality, quantity and photoperiod differ from the natural environment. The spectrum provided by the current lighting technology, high-pressure sodium lamp (HPSL), differs considerably from that of solar radiation. The major plant-mediated effects on arthropods were predicted to result from (a) extended photoperiods and lower light integrals, (b) the attenuation of ultraviolet (UV) wavelengths, particularly UV-B, (c) the high red: far-red (R : FR) ratio and lower blue : red (B : R) in comparison with solar radiation and (d) the high proportion of yellow wavelengths during winter months. Of these light factors (a–d) (ceteris paribus), (a) and (b) were hypothesised to result in increased performance of herbivores in winter months, whereas the high R : FR ratio decreased herbivore performance or not affected it, at least when interlights are used. The predictions obtained on the basis of this review are also discussed in relation to the modifying factors prevailing in these production environments: enriched CO2 levels, high nutrient amounts, optimised irrigation and temperatures optimal for plants' needs. Based on the carbon/nitrogen and growth/differentiation balance theories, these modifying factors tend to produce plants that allocate most resources to growth at the expense of defensive secondary metabolism and physicochemical defensive structures. At the end, this review discusses knowledge gaps and future research prospects, in which light-emitting diodes, the emerging lighting technology, play an important role by enabling the targeted manipulation of plant responses to different wavelengths.

Tropospheric ozone (O3) is an important secondary air pollutant formed as a result of photochemical reactions between primary pollutants, such as nitrogen oxides (NOx), and volatile organic compounds (VOCs). O3 concentrations in the lower atmosphere (troposphere) are predicted to continue increasing as a result of anthropogenic activity, which will impact strongly on wild and cultivated plants. O3 affects photosynthesis and induces the development of visible foliar injuries, which are the result of genetically controlled programmed cell death. It also activates many plant defense responses, including the emission of phytogenic VOCs. Plant emitted VOCs play a role in many eco-physiological functions. Besides protecting the plant from abiotic stresses (high temperatures and oxidative stress) and biotic stressors (competing plants, micro- and macroorganisms), they drive multitrophic interactions between plants, herbivores and their natural enemies e.g., predators and parasitoids as well as interactions between plants (plant-to-plant communication). In addition, VOCs have an important role in atmospheric chemistry. They are O3 precursors, but at the same time are readily oxidized by O3, thus resulting in a series of new compounds that include secondary organic aerosols (SOAs). Here, we review the effects of O3 on plants and their VOC emissions. We also review the state of current knowledge on the effects of ozone on ecological interactions based on VOC signaling, and propose further research directions.

Monoterpenes are biogenic volatile organic compounds (BVOCs) which play an important role in plant adaptation to stresses, atmospheric chemistry, plant–plant and plant–insect interactions. In this study, we determined whether ozonolysis can influence the monoterpenes in the headspace of cabbage. The monoterpenes were mixed with an air-flow enriched with 100, 200 or 400 ppbv of ozone (O 3 ) in a Teflon chamber. The changes in the monoterpene and O 3 concentrations, and the formation of secondary organic aerosols (SOA) were determined during ozonolysis. Furthermore, the monoterpene reactions with O 3 and OH were modelled using reaction kinetics equations. The results showed that all of the monoterpenes were unequally affected: α -thujene, sabinene and d -limonene were affected to the greatest extend, whereas the 1,8-cineole concentration did not change. In addition, plant monoterpene emissions reduced the O 3 concentration by 12–24%. The SOA formation was dependent on O 3 concentration. At 100 ppbv of O 3 , virtually no new particles were formed but clear SOA formation was observed at the higher ozone concentrations. The modelled results showed rather good agreements for α -pinene and 1,8-cineole, whereas the measured concentrations were clearly lower compared to modelled values for sabinene and limonene. In summary, O 3 -quenching by monoterpenes occurs beyond the boundary layer of leaves and results in a decreased O 3 concentration, altered monoterpene profiles and SOA formation.

During development, activation of Cl(-)-permeable GABA(A) receptors (GABA(A)-R) excites neurons as a result of elevated intracellular Cl(-) levels and a depolarized Cl(-) equilibrium potential (E(Cl)). GABA becomes inhibitory as net outward neuronal transport of Cl(-) develops in a caudal-rostral progression. In line with this caudal-rostral developmental pattern, GABAergic anticonvulsant compounds inhibit motor manifestations of neonatal seizures but not cortical seizure activity. The Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) facilitates the accumulation of Cl(-) in neurons. The NKCC1 blocker bumetanide shifted E(Cl) negative in immature neurons, suppressed epileptiform activity in hippocampal slices in vitro and attenuated electrographic seizures in neonatal rats in vivo. Bumetanide had no effect in the presence of the GABA(A)-R antagonist bicuculline, nor in brain slices from NKCC1-knockout mice. NKCC1 expression level versus expression of the Cl(-)-extruding transporter (KCC2) in human and rat cortex showed that Cl(-) transport in perinatal human cortex is as immature as in the rat. Our results provide evidence that NKCC1 facilitates seizures in the developing brain and indicate that bumetanide should be useful in the treatment of neonatal seizures.

Periventricular leukomalacia is a form of hypoxic–ischemic cerebral white matter injury seen most commonly in premature infants and is the major antecedent of cerebral palsy. Glutamate receptor-mediated excitotoxicity is a predominant mechanism of hypoxic–ischemic injury to developing cerebral white matter. We have demonstrated previously the protective effect of AMPA–kainate-type glutamate receptor blockade in a rodent model of periventricular leukomalacia. The present study explores the therapeutic potential of glutamate receptor blockade for hypoxic–ischemic white matter injury. We demonstrate that AMPA receptors are expressed on developing human oligodendrocytes that populate fetal white matter at 23–32 weeks gestation, the period of highest risk for periventricular leukomalacia. We show that the clinically available anticonvulsant topiramate, when administered post-insultin vivo, is protective against selective hypoxic–ischemic white matter injury and decreases the subsequent neuromotor deficits. We further demonstrate that topiramate attenuates AMPA–kainate receptor-mediated cell death and calcium influx, as well as kainate-evoked currents in developing oligodendrocytes, similar to the AMPA–kainate receptor antagonist 6-nitro-7-sulfamoylbenzo-(f)quinoxaline-2,3-dione (NBQX). Notably, protective doses of NBQX and topiramate do not affect normal maturation and proliferation of oligodendrocytes eitherin vivoorin vitro. Taken together, these results suggest that AMPA–kainate receptor blockade may have potential for translation as a therapeutic strategy for periventricular leukomalacia and that the mechanism of protective efficacy of topiramate is caused at least in part by attenuation of excitotoxic injury to premyelinating oligodendrocytes in developing white matter.

Objective: To compare gap junction expression and intercellular coupling in wildtype neonatal cardiac myocytes to those from mice lacking the most abundant cardiac gap junction protein (connexin43, Cx43). Methods: Northern and Western blots compared connexin mRNA and protein levels, immunocytochemistry evaluated connexin distribution in neonatal Cx43 null(−/−), heterozygous(+/−) and wildtype(+/+) mouse hearts. Ca2+ imaging, dye coupling and electrophysiological methods evaluated intercellular communication. Results: Similar levels of Cx40 and Cx45 were detected in all genotypes, although in adult cardiac tissue from wildtype mice, Cx43 expression was higher than in heterozygotes. After culturing dissociated cells for 3–4 days, cardiocytes beat spontaneously; in Cx43(+/+) and (+/−) cultures, the beating was generally quite synchronous. In Cx43(−/−) mice, interbeat intervals were on average twice as long and more variable than in Cx43(+/+) or Cx43(+/−) cultures. Junctional conductance was lower by about 60% in Cx43(−/−) as compared to Cx43(+/−) and (+/+) littermates; Lucifer Yellow dye coupling was virtually absent in Cx43(−/−) cardiomyocytes but was comparably strong in wildtype and heterozygous siblings. Macroscopic junctional conductance measurements on Cx43(−/−) cardiocytes showed slightly stronger voltage sensitivity in these cells than in Cx43(+/+) cardiocytes. Unitary junctional conductance measurements revealed distinct populations of channels contributing to macroscopic conductance for Cx43(+/+) and Cx43(−/−) genotypes. Conclusions: In Cx43-deficient cardiac myocytes, the expression of other connexins only partially compensates for the functional loss, with dye coupling and spontaneous beating being strongly impaired.

Two organic ligands, N,N′-bis(2-pyridylmethyl)urea, “2u”, and N,N′-bis(3-pyridylmethyl)oxalamide, “3o”, were employed in the synthesis of three new extended structures. The reaction between EuCl3 · 6H2O (1) and 2u afforded a molecular species, Eu(2uH2)Cl5, which assembled in one-dimensional chains by hydrogen bonding. When EuCl3 · 6H2O was replaced by TbCl3 · 6H2O, the reaction with 2u yielded another molecular compound, Tb(2uH2)Cl5, having the same structural features as 1. 3o reacted with EuCl3 · 6H2O and formed compound 3, [Eu(3oH)(H2O)2Cl3]Cl, in which the 3o ligand acts as a bridge between the metal centers to form an infinite one-dimensional chain structure. The chains are further linked in three dimensions by hydrogen bonds and π–π stacking. Luminescence data for all three compounds are presented.

Three new organic–inorganic coordination polymers, each adopting a different structural motif, were obtained from the CdI2/pyrazinecarboxylic acid system. Syntheses and X-ray structural determinations are presented. The reaction between CdI2 and 2-pyrazinecarboxylic acid (abbreviated pyzcaH) afforded a one-dimensional chain-like structure, [CdI2(PyzcaH)(H2O)]n (1). When 2-pyrazinecarboxylic acid was replaced by Cu(2-pyrazinecarboxylate)2, the reaction yielded a two-dimensional framework polymer, [CdI(Pyzca)(H2O)]n (2). The reaction of CdI2 and 2-methylpyrazine-5-carboxylic acid (abbreviated MePyzcaH) resulted in the formation of a different coordination polymer, [CdI(MePyzca)(H2O)1.5]n (3), which adopts a one-dimensional chain structure. These new coordination polymers all assemble into three-dimensional structures via networks of hydrogen bonds.

We compared the effects of manipulations during week 1 vs week 2 of life on the propensity to self-administer cocaine. Pups received daily subcutaneous saline injections, were handled briefly, or remained undisturbed during their respective treatment periods. Animals handled during the second week of life exhibited increased locomotor response to novelty when tested on postnatal day (PND) 48, compared to all other groups. Rats were implanted with jugular catheters on PND 70 and then given the opportunity to self-administer (0.125 mg/kg/infusion) cocaine for 5 consecutive days (1 h sessions). The dose was then raised to 0.25 mg/kg/infusion for 5 days and to 0.5 mg/kg/infusion for the final 5 days of testing. Only animals manipulated during the second week of life acquired drug-taking behavior. These effects were both stimulus- and gender-specific. Females handled during the second week of life acquired cocaine self-administration (SA) at the lowest dose, and females injected during the second week of life acquired at the intermediate dose. Males injected during the second week of life showed a similar, but more variable, drug-taking pattern. There were no group differences in serum corticosterone response to novelty, although relative to undisturbed animals and those manipulated in the first week of life, female animals manipulated during the second week of life had lower basal expression of hippocampal glucocorticoid receptor mRNA in adulthood. We conclude that the second week of life in the rodent is a sensitive period during which manipulations result in a more vulnerable phenotype for the acquisition of cocaine SA.

Four new inorganic–organic polymeric materials have been synthesized by reacting the metal containing building block, Cu(pyzca)2, with cadmium chloride. All resulting polymers have both metals incorporated in the structure and display a variety of structural motifs, ranging from one-dimensional chains to complicated three-dimensional networks. The first compound, [Cu(Pyzca)2(H2O)CdCl2(H2O)·H2O]n (1) is a one-dimensional double chain. The next two compounds, [Cu(Pyzca)2(H2O)2Cd2Cl4(H2O)2]n (2) and [Cu(Pyzca)2(H2O)Cd2Cl4(H2O)2·3H2O]n (3), assemble in a two-dimensional brick-wall network, while the fourth, [Cu(Pyzca)2Cd2Cl4]n (4), features an intricate three-dimensional network. Synthesis, X-ray structure determinations, and the influence of water molecules coordinated to the copper centers on the coordination geometry and overall extended structure are discussed.

The manganese-containing molecular building block Mn(2-methylpyrazine-5-carboxylato)2·(H2O)2 (1, triclinic, P-1, a=7.2042(6) A, b=7.4067(6) A, c=13.9982(12) A, α=87.205(2)°, β=81.162(2)°, γ=80.517(2)°, Z=2) was prepared and used in the synthesis of a new mixed-metal organic-inorganic polymeric material. The reaction between 1 and Rh2(OAc)4 resulted in the formation of catena-poly{[Mn(MePyzca)2(MeOH)2][Rh2(OAc)4]}·2MeOH (2, monoclinic, C2/c, a=29.711(3) A, b=7.9124(8) A, c=15.5028(15) A, β=109.212(2)°, Z=4), where the Mn(MePyzca)2(MeOH)2 building blocks are linked by Rh2(OAc)4 dimers into a one-dimensional zigzag chain structure. The magnetic susceptibility for 2 follows the Curie law, with no indication of long range magnetic order. Synthesis, X-ray structure determination and magnetic properties are presented.

Four new organic/inorganic coordination polymers, [Cd(C(10)H(8)N(2))(2)(H(2)O)(2)(NO(3))(2)](n)(1), [Co(C(10)H(8)N(2))(H(2)O)NO(3)CH(3)OH](n)(2), [Cu(C(10)H(8)N(2))(CH(3)OH)(NO(3))(2)](n) (3), and [Cu(C(10)H(8)N(2))(hfac)(2)](n)(4), were synthesized by using the rigid ligand 1,2-bis(3-pyridyl)ethyne (3,3'-DPA). Complex 1 crystallizes in space group P2/n: a = 12.462(2) A, b = 9.485(1) A, c = 13.383(2) A, beta = 96.629(2) degrees, V = 1559.6(3) A(3), Z = 4. Complex 2 crystallizes in space group Fddd: a = 9.248(4) A, b = 19.982(7) A, c = 35.093(16) A, V = 6485.0(4) A(3), Z = 8. Complex 3 crystallizes in space group I2/a: a = 18.315(2) A, b = 8.517(1) A, c = 20.494(3) A, beta = 104.042(2) degrees, V = 3101.2(7) A(3), Z = 8. Complex 4 crystallizes in space group P21/c: a = 6.576(1) A, b = 16.189(1) A, c = 11.653(1) A, beta = 91.337(1) degrees, V = 1240.3(2) A(3), Z = 2. The coordination polymers display a variety of structural architectures, ranging from sinusoidal and zigzag chains (1, 3, 4) to two-dimensional channel-type architectures (2). The effects of the orientation of the nitrogen atom in the pyridine rings on the resultant structures are discussed.

The cobalt-containing molecular building block Co(2-pyrazinecarboxylato)2·(H2O)2 (1) was prepared and used in the synthesis of a new mixed metal organic–inorganic polymeric material. The reaction between 1 and AgNO3 resulted in the formation of {Ag[Co(pyzca)2(H2O)(NO3)]}n (2, orthorhombic, Pbca; a = 12.9991(9), b = 7.7977(5), c = 27.7847(17) A, Z = 8), where Co(C5H3N2O2)2(H2O)(NO3) building blocks are linked by Ag atoms into a one-dimensional linear chain structure. The chains are linked into a three-dimensional framework via weak Ag + ··· (NO3) − interactions and “bifurcated” hydrogen bonds. The new coordination polymer exhibits thermal stability up to 200 ◦ C. The magnetic susceptibility for 2 follows the Curie law, with no indication of long range magnetic order. Synthesis, X-ray structure determination, thermogravimetric analysis and magnetic properties are presented.  2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.

Clinical and epidemiological studies have found an association between aversive experiences early in life and an increased risk for depression, anxiety and substance abuse. In order to elucidate the mechanisms by which adverse life events are translated into behavioral and psychological abnormalities, we used a rat model to study the impact of chronic injection and 24 h maternal deprivation on the developing rat brain. Specifically, we investigated the regulation of molecules related to the 5-HT (5-HT) system and studied the effect of desipramine administration on animals that were maternally deprived (DEP) on day 13 of life compared with non-deprived animals. We found that maternal deprivation caused an enhanced corticosterone response to an acute stress. Maternally deprived animals also showed a decrease in corticosteroid receptors and an increase in 5-HT 1A and 1B receptors restricted to the CA1 region of the hippocampus. Desipramine prevented the maternal deprivation induced up-regulation of the 5-HT 1B receptor and the enhanced adrenocortical response observed in these animals. Interestingly, non-deprived animals receiving chronic injections showed a decrease in hippocampal 5-HT1B receptor mRNA. At 80 days of age, a group of animals that were treated as infants were given the option of drinking from two identical water bottles, one bottle contained tap water, while the second contained ethanol at increasing concentrations. Animals that received chronic injections during the newborn period consumed more alcohol than those that were not injected. On the other hand, maternal deprivation did not have an impact on alcohol consumption. Alcohol preference has implications to the organism since studies of drug self-administration in laboratory animals have shown that ethanol ingestion is positively related to the use of other drugs, principally opioids and psychostimulants. Our findings suggest that the quality and/or chronicity of early life stressors can influence the neurobiological substrates that may trigger and/or predispose individuals to substance abuse in adulthood.

The copper containing building block, Cu(C6H5N2O2)2·H2 O( 1) was used in the synthesis of four new mixed-valent organic–inorganic coordination polymers, each of which adopted a different structural motif. Synthesis, X-ray structure determinations, thermogravimetric analyses and magnetic properties are presented. The reaction between 1 and CdCl2 afforded a one-dimensional chain structure, [Cu(C6H5N2O2)2(H2O)2Cu2Cl2(H2O)2]n (2). When CdCl2 was replaced by CuCl, the reaction yielded a polymer, [Cu(C6H5N2O2)2(H2O)2Cu2Cl2(H2O)2]n having the same empirical formula, but a completely different two-dimensional framework (3). The reaction of CdBr2 and 1 resulted in the formation of two different coordination polymers: [Cu(C6H5N2O2)2(H2O)2Cu(C6H5N2O2)2Cu2Br2·3(H2O)]n (4) as a minor phase and [Cu(C6H5N2O2)2Cu2Br2·]n (5) as the major phase. Compound 4 adopts a two-dimensional structure, while 5 is three-dimensional. The structural classification of these Cu(I) containing coordination polymers is discussed. These new coordination polymers feature mixed-valent Cu(I)–Cu(II) frameworks and exhibit impressive thermal stability (the frameworks collapse between 236 and 246 °C). The magnetic susceptibilities for 2, 3 and 5 followed the Curie law, indicating simple paramagnetic behavior. © 2001 Elsevier Science B.V. All rights reserved.

The present study investigated the effect of prenatal dexamethasone (Dex) exposure on early perinatal events, hippocampal function, and response to stress. Pregnant rats received Dex in the evening water (2.5 μg/ml) or tap water (Veh) from gestational day 15until delivery. On the day of parturition, pups were randomized, cross-fostered, and reduced to eight or nine per dam. Four groups resulted: Veh-Veh (offspring exposed to Veh in utero, rearing mother treated with Veh during gestation), Veh-Dex, Dex-Veh, and Dex-Dex. Spatial visual memory was evaluated with the Morris water maze. The corticosterone response to restraint stress was examined, and the expression of hippocampal glucocorticoid and mineralocorticoid receptors mRNA was determined by in situ hybridization. Exposure to Dex caused restlessness in mothers, low birth weights, and poor weight gain in the offspring. The Dex-Dex males had impaired spatial learning, inability to rapidly terminate the adrenocortical response to stress, and decreased hippocampal glucocorticoid receptor (GR) mRNA expression. In contrast, Dex-exposed animals reared by Veh-treated mothers had adequate spatial learning, enhanced glucocorticoid feedback, and increased hippocampal GR mRNA. We conclude that the environment provided by a healthy mother during the postnatal period can prevent the detrimental effects of prenatal Dex administration on cognition, GR mRNA expression of the hippocampus, and the quality of the stress response.

Leukocyte chemoattractants are known to stimulate signaling pathways that involve Rho family GTPases. Direct evidence for the regulation of the leukocyte cytoskeleton by Rho GTPases and their effector targets is limited. The p21-activated kinases (PAKs) are specific targets of activated GTP-bound Rac and Cdc42, and have been proposed as regulators of chemoattractant-driven actin cytoskeletal changes in fibroblasts. PAK1 co-localizes with F-actin to cortical actin structures in stimulated fibroblasts, and activated PAK1 mutants induce membrane ruffling and polarized cytoskeletal rearrangements. We investigated whether PAK1 was associated with remodeling ofthe actin cytoskeleton in activated human neutrophils. We monitored the redistribution of PAK1 and F-actin into the actin cytoskeleton after stimulation of human neutrophils with the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP) or the particulate stimulus, opsonized zymosan (OZ). PAK1 exhibited a similar distribution as F-actin in fMLP-stimulated leukocytes, localizing in membrane ruffles and to lamellipodia at the leading edge of polarized cells. Addition of OZ induced phagocytic uptake of this particulate stimulus, and PAK1 re-localized to the F-actin-rich pseudopodia and phagocytic cups associated with this process. Once the OZ was internalized, there was little PAK1 localized around the ingested particles, suggesting that PAK1 may be regulating the cytoskeletal extensions and events required for engulfment of bacteria, but not the subsequent steps of internalization. Localization of PAK1 and F-actin in cytoskeletal structures was abolished by the actin polymerization inhibitor cytochalasin D and the phosphatidylinositol 3-kinase inhibitor wortmannin. Our data suggest that PAK1 may regulate a subset of cytoskeletal dynamics initiated by chemoattractant and phagocytic stimuli in human neutrophils. J. Leukoc. Biol. 66: 521–527; 1999.

Two different types of corticoid receptor molecules bind circulating corticosterone in brain: mineralocorticoid receptors (MR) and glucocorticoid receptors. MR exhibit the highest affinity for the endogenous glucocorticoid in the rat, corticosterone. During development, low corticosterone levels influence neurogenesis, and these effects are probably MR mediated. Three MR complementary DNA clones, α, β, and γ, have been identified in the rodent. All of these MR complementary DNA clones have identical coding regions, but differ significantly at the 5′-untranslated end. Although the functional significance of these three messenger RNA (mRNA) species remains unknown, one hypothesis is that they reflect the ability of the brain to regulate the expression of MR, allowing multiple factors to differentially control transcription in a tissue- and time-specific manner. To investigate this possibility, we examined the presence of these distinct mRNA forms in the developing rat hippocampus (HC). In situ hybridization with specific α, β, and γ complementary RNA probes was performed in the HC of 3-, 5-, 7-, 12-, 14-, 28-, 35-, and 65-day-old animals. We found that there is differential expression of these forms in each of the HC subfields from infancy to adulthood. γ expression appears to be associated with periods of cell birth and increased axonal sprouting. β expression, on the other hand, may be best linked to periods of synaptogenesis, growth of commissural and associative terminal fields, and possibly active pruning. To explore the possibility that the differential gene expression may be related to corticosterone environment, adrenalectomy was performed. A rapid modulation of the MR mRNA variants (14 h) in an age- and site-specific fashion was seen. These findings suggest that the variation in expression and regulation during development of the multiple MR transcripts could reflect a complex pattern of developmental regulation that may involve a multitude of factors unique to each postnatal age and to the different neuronal populations within the hippocampal formation.

Incorporation of fluorous ponytails such as polyfluorinated alkyl residues (CH2)m(CF2)nCF3 leads to a novel class of bright rhodamine-based fluorescence dyes. These dyes combine the excellent photophysical properties of the frequently used rhodamine dyes with the unique features of “light” fluorous molecules. One of those features is the possibility to separate substances utilizing fluorous solid-phase extraction (F-SPE), which is based on the specific intermolecular interaction between fluorous compounds. Thus, molecules, which are labeled with these new dyes, are not only accessible to fluorescence experiments, but can also be easily purified (via so-called FluoroFlash columns) prior to use. The dyes were bound to a cell penetrating peptoid (polycationic oligo(N-substituted) glycine) on solid supports. These conjugates were purified with F-SPE before their photophysical and biological properties were investigated.

In this work, feeding policies aimed to avoid cellular stress responses as indicated by an increase in ATP-dependent proteolysis are tested. A set of experiments was carried out where glucose, IPTG (inducer), and phenylalanine (rate-limiting precursor) were added gradually in a fed-batch fashion. A significant increase in CAT activity was found compared with pulse-induction. In addition, there was a substantial increase in the rate of CAT synthesis as well as in the final specific CAT activity when phenylatanine and the inducer were added simultaneously. CAT degradation was confirmed through Western blotting analysis. Protease analysis (SDS-GPAGE) indicated lower proteolytic activity for the IPTG and phenylalanine fed-batch cases. GroEL immunoas-says indicated that amplification of stress proteins occurred upon CAT induction. This research impacts the yield of soluble cytoplasmic proteins in Escherichia coli and suggests that metabolically based induction/feeding policies are beneficial. (c) 1995 John Wiley & Sons Inc.

The title compound, [Pd(C14H12N4O2)]·H2O·0.5CHCl3, features a Pd2+ metal center chelated by the four N atoms of the organic ligand N,N′-bis(2-pyridyl­methyl)­ox­amide. The asymmetric unit is composed of two similar independent Pd(C14H12N4O2) mol­ecules, two water mol­ecules and one mol­ecule of CHCl3. Hydro­gen bonds between the carbonyl O atoms of the chelating ligand and the water molecules link the mol­ecules into two-dimensional layers parallel to the crystallographic ac plane.

BACKGROUND: Neonatal seizures can result in chronic epilepsy and long-term behavioral and cognitive deficits. Levetiracetam (LEV), an antiepileptic drug that binds to the synaptic vesicle protein 2A (SV2A), has been increasingly used off-label for the therapy of neonatal seizures. Preclinical data regarding the acute or long-term efficacy of LEV are lacking. METHODS: We tested the anticonvulsant efficacy of LEV in a rat model of hypoxia-induced neonatal seizures. In addition, we evaluated the protective effects of postnatal day (P)10 LEV treatment on later-life kainic acid (KA)–induced seizure susceptibility and seizure-induced neuronal injury. Western blot and immunohistochemistry were used to assess the developmental regulation of SV2A in the rat and human brain. RESULTS: LEV pretreatment at P10 significantly decreased the cumulative duration of behavioral and electrographic seizures at both 25 and 50 mg/kg. At P40, KA-induced seizures and neuronal loss were significantly diminished in rats previously treated with LEV. LEV target SV2A is present in both neonatal rat and human brain and increases steadily to adulthood. CONCLUSION: LEV suppressed acute seizures induced by perinatal hypoxia and diminished later-life seizure susceptibility and seizure-induced neuronal injury, providing evidence for disease modification. These results support consideration of a clinical trial of LEV in neonatal seizures.

Cerebral white matter injury in premature infants, known as periventricular leukomalacia (PVL), is common after hypoxia–ischemia (HI). While ionotropic glutamate receptors (iGluRs) can mediate immature white matter injury, we have previously shown that excitotoxic injury to premyelinating oligodendrocytes (preOLs) in vitro can be attenuated by group I metabotropic glutamate receptor (mGluR) agonists. Thus, we evaluated mGluR expression in developing white matter in rat and human brain, and tested the protective efficacy of a central nervous system (CNS)-penetrating mGluR agonist on injury to developing oligodendrocytes (OLs) in vivo. Group I mGluRs (mGluR1 and mGluR5) were strongly expressed on OLs in neonatal rodent cerebral white matter throughout normal development, with highest expression early in development on preOLs. Specifically at P6, mGluR1 and mGLuR5 were most highly expressed on GalC-positive OLs compared to neurons, axons, astrocytes and microglia. Systemic administration of (1S,3R) 1-aminocyclopentane-trans-1,3,-dicarboxylic acid (ACPD) significantly attenuated the loss of myelin basic protein in the white matter following HI in P6 rats. Assessment of postmortem human tissue showed both mGluR1 and mGluR5 localized on immature OLs in white matter throughout development, with mGluR5 highest in the preterm period. These data indicate group I mGluRs are highly expressed on OLs during the peak period of vulnerability to HI and modulation of mGluRs is protective in a rodent model of PVL. Group I mGluRs may represent important therapeutic targets for protection from HI-mediated white matter injury.

Potent glucocorticoids (GC) administered early in life have improved premature infant survival dramatically. However, these agents may increase the risk for physical, neurological and behavior alterations. Anxiety, depression and attention difficulties are commonly described in adolescent and young adult survivors of prematurity. In the present study we administered vehicle, dexamethasone, or hydrocortisone to Sprague-Dawley rat pups on postnatal days 5 and 6, mimicking a short term clinical protocol commonly used in human infants. Two systems that are implicated in the regulation of stress and behavior were assessed: the limbic-hypothalamic-pituitary-adrenal axis [LHPA; glucocorticoid and mineralocorticoid receptors within] and the Serotonin (5-HT) system. We found that as adults, male Sprague-Dawley pups treated with GC showed agent specific altered growth, anxiety-related behavior, changes in corticoid response to novelty and gene expression changes within LHPA and 5-HT-related circuitry. The data suggest that prolonged GC-receptor stimulation during the early neonatal period can contribute to the development of individual differences in stress response and anxiety-related behavior later in life.

In the central nervous system, adrenal steroids bind to two different types of corticosteroid receptors: glucocorticoid (GR) or mineralocorticoid (MR). In vitro biochemical and autoradiographic techniques have been used to infer GR and MR protein abundance in the hippocampus. Adrenalectomy (ADX) is routinely performed to measure the normal receptor number in absence of corticosterone (B), which would otherwise interfere with the binding reaction, The developing rodent has low basal B levels until the third week of life. We were interested in whether removal of circulating B may have a greater impact in the developing hippocampus than in the adult animal. In this study we examined the effect of a 14-h ADX on hippocampal GR and MR binding capacity (B(max)) by standard binding techniques and on gene expression by in situ hybridization. ADX was performed on Day 6, 10, 14, 18, 22, 28, 35, and 45 and on adult animals. GR B(max) increased from Day 6 to adult levels by Day 22 (d6 = 159.0 +/- 27; d22 = 369.1 +/- 43; a = 344.8 +/- 23, fmol/mg protein +/- SE). In contrast, MR B(max) had adult levels on Day 6 and increased above these until Day 45, when it decreased and approached adult concentrations (d6 = 83.2 +/- 22; d45 = 123 +/- 23; a = 76.9 +/- 13, fmol/mg protein +/- SE). The greatest absolute increase for both receptors occurred between Days 22 and 45 and correlated with increases in GR and MR gene expression. Moreover, age- and region-specific changes were evident in the developing hippocampus. In addition, the adult animal also exhibited an MR mRNA upregulation after 14 h of adrenalectomy. We propose extreme caution when interpreting GR and MR B(max) values obtained after short-term adrenalectomy in both adult and developing animals since upregulation of these genes is evident in this short time frame.

In this work, effective feeding schemes that would minimize stress responses to cloned-protein overexpression are investigated. The cloned-protein (chloramphenicolacetyl-transferase, CAT) contains a high aromatic amino acid content, most notably a high phenylalanine content. Experiments performed on Escherichia coli RR1 [pBR329] (constitutive promoter) and E. coli JM105 [pSH101] (inducible promoter) demonstrated that phenylalanine addition increases the rate of synthesis and yield of CAT. A previous study correlating inducer strength with CAT expression in E. coli JM105 [pSH101] indicated that the highest expression rate was accompanied by the highest apparent rate of protein degradation. In this work, the combined addition of isopropyl-beta-D-thiogalactopyranoside (IPTG) and phenylalanine at intermediate levels resulted in substantial increase of CAT synthesis and partial reduction of protein degradation. Furthermore, transmission electron micrographs verified the absence of inclusion bodies, which, along with proteases, were suspected to reduce protein activity. The research demonstrates that significant enhancement in production and stability of heterologous proteins is possible by designing feeding strategies that incorporate knowledge of the interaction between primary cellular metabolism and foreign protein expression.

The two new luminescent coordination polymers HgCl2(C31H24N2)·CH2Cl2 (1) and HgBr2(C31H24N2)·CH2Cl2 (2) feature helical zigzag chains intertwined in bundles of three. The luminescent properties of the isostructural compounds are due to the fluorene-based ligand 9,9-bis-ethyl-2,7-di-(4-pyridyl)ethynylfluorene and are red-shifted relative to those of the free ligand.

Inducible terpenes and lipoxygenase pathway products, e.g., green-leaf volatiles (GLVs), are emitted by plants in response to herbivory. They are used by carnivorous arthropods to locate prey. These compounds are highly reactive with atmospheric pollutants. We hypothesized that elevated ozone (O(3)) may affect chemical communication between plants and natural enemies of herbivores by degrading signal compounds. In this study, we have used two tritrophic systems (Brassica oleracea-Plutella xylostella-Cotesia plutellae and Phaseolus lunatus-Tetranychus urticae-Phytoseiulus persimilis) to show that exposure of plants to moderately enhanced atmospheric O(3) levels (60 and 120 nl l(-1)) results in complete degradation of most herbivore-induced terpenes and GLVs, which is congruent with our hypothesis. However, orientation behavior of natural enemies was not disrupted by O(3) exposure in either tritrophic system. Other herbivore-induced volatiles, such as benzyl cyanide, a nitrile in cabbage, and methyl salicylate in lima bean, were not significantly reduced in reactions with O(3). We suggest that more atmospherically stable herbivore-induced volatile compounds can provide important long-distance plant-carnivore signals and may be used by natural enemies of herbivores to orientate in O(3)-polluted environments.