Pentachlorophenol Dechlorination in Fluidized-Bed Reactors under Methanogenic Conditions

The reductive dechlorination of chlorophenols was studied in three fluidized-bed reactors (FBRs) with respect to enrichment, pathways, complete dechlorination, and overall performance. The methanogenic consortia, developed by previous researchers in our laboratory, have been further enriched by reducing the ratio of substrate to pentachlorophenol (PCP) and increasing the PCP loading. The performance of the consortia was improved, and complete dechlorination at high PCP loading rates was observed, reaching a PCP loading of 1227 µmol/L d with 99% chlorophenol removal. The dechlorination rates in the reactors for chlorophenol (CP) congeners were obtained and were used to evaluate the performance of the three consortia and to quantitatively estimate the fates of these chlorophenols in the reactors. The consortium with the best performance was further investigated in bottle tests by treatment with heat and metabolic inhibitors to examine chlorophenol degradation and to characterize the CP degraders. The degradation of all monochlorophenols was completely inhibited after heat treatment, but the degradation of all other tested chlorophenols was hardly affected by heat treatment, indicating that spore-forming bacteria likely were involved in dechlorination. Addition of sulfate negatively affected CP degradation, but addition of molybdate reduced the effect of sulfate. Tests with 2-bromoethanesulfonic acid and vancomycin indicated that bacteria were responsible for chlorophenol degradation in the consortium.     

Acute Effects of Pathogenic Simian-Human Immunodeficiency Virus Challenge on Vaccine-Induced Cellular and Humoral Immune Responses to Gag in Rhesus Macaques

Simian-human immunodeficiency virus (SHIV) infection in macaques provides a convenient model for testing vaccine efficacy and for understanding viral pathogenesis in AIDS. We immunized macaques with recombinant, Salmonella typhimurium (expressing Gag) or soluble Gag in adjuvant to generate T-cell-dependent lymphoproliferative or serum antibody responses. Immunized animals were challenged by intrarectal inoculation with SHIV89.6PD. Virus infection was accompanied by rapid losses of lymphoproliferative responses to Gag or phytohemagglutinin. By 8 weeks, mitogen responses recovered to near normal levels but antigen-specific immunity remained at low or undetectable levels. Serum antibody levels were elevated initially by virus exposure but soon dropped well below levels achieved by immunization. Our studies show a rapid depletion of preexisting Gag-specific CD4⁺ T cells that prevent or limit subsequent antiviral cellular and humoral immune responses during acute SHIV infection.     

Induction of CCK mRNA levels in the limbic-hypothalamic circuit: Time course and site-specific effects of estrogen

Estrogenic regulation of cholecystokinin (CCK) and its receptors is correlated with the initiation and termination of lordosis behavior. To understand the effect of circulating estrogen concentration on the temporal aspects of CCK mRNA expression in the posterodorsal medial amygdaloid nucleus (MeApd) and the central part of the medial preoptic nucleus (MPNc) of the limbic-hypothalamic circuit, ovariectomized female rats were treated with a 10 mm Silastic™ capsule filled with estradiol, a bolus injection of 50 μg estradiol benzoate or 2 μg estradiol benzoate every 4 days for five “cycles.” In situ hybridization was used to compare the relative changes of CCK mRNA levels at 0 h to levels measured at 6, 12, 24, 48, 72, or 96 h after estrogen administration. In the MPNc and the MeApd, the 10-mm capsule significantly increased and maintained CCK mRNA levels from 6 to 96 h. The range of the increase was 3.0–5.1-fold in the MPNc and 2.8–5.0 in the MeApd. The 50-μg injections significantly increased and maintained CCK mRNA levels in the MPNc from 12 to 96 h (range of the increase 2.4–4.1-fold) and in the MeApd from 24 to 96 h (range of the increase 2.2–2.8-fold). The repeated administration of 2 μg estrogen induced a significant increase of message levels in the MPNc at 12 and 24 h that were 4.2- and 4.7-fold, respectively. In the MeApd this estrogen treatment did not significantly increase CCK mRNA. These studies demonstrate that small doses (2 μg) of estrogen that mimic the pattern and circulating levels of estrogen dramatically stimulate CCK mRNA levels in the limbic-hypothalamic circuit. To further study this steroid stimulation, ovariectomized female rats were implanted with estradiol-filled cannulae into the bed nucleus of the stria terminalis or MeA. Estrogen elevated CCK mRNA levels locally in each nucleus. Implants in the bed nucleus also elevated CCK mRNA levels in the MeApd indicating that physiologic estrogen stimulation of CCK in the MeApd is the result of both local and distal transsynaptic elevation of CCK mRNA levels. The site-specific induction of CCK mRNA levels within the limbic-hypothalamic nuclei provides another important facet of estrogenic modulation of CCK induction. © 1996 John Wiley & Sons, Inc.     

Quantitative characterization of the mechanism of action and impact of a ‘proteolysis-permitting’ anti-PCSK9 antibody

A recent report described a novel mechanism of action for an anti-proprotein convertase subtilisin-kexin type 9 (PCSK9) monoclonal antibody (LY3015014, or LY), wherein the antibody has improved potency and duration of action due to the PCSK9 epitope for LY binding. Unlike other antibodies, proteolysis of PCSK9 can occur when LY is bound to PCSK9. We hypothesized that this allowance of PCSK9 cleavage potentially improves LY efficiency through two pathways, namely lack of accumulation of intact PCSK9 and reduced clearance of LY. A quantitative modeling approach is necessary to further understand this novel mechanism of action. We developed a mechanism-based model to characterize the relationship between antibody pharmacokinetics, PCSK9 and LDL cholesterol levels in animals, and used the model to better understand the underlying drivers for the improved efficiency of LY. Simulations suggested that the allowance of cleavage of PCSK9 resulting in a lack of accumulation of intact PCSK9 is the major driver of the improved potency and durability of LY. The modeling reveals that this novel ‘proteolysis-permitting’ mechanism of LY is a means by which an efficient antibody can be developed with a total antibody dosing rate that is lower than the target production rate. We expect this engineering approach may be applicable to other targets and that the mathematical models presented herein will be useful in evaluating similar approaches.     

A rapid method for determining dynamic binding capacity of resins for the purification of proteins

Biolayer interferometry is a novel method for quantifying macromolecules, such as proteins, in solution. The presence of other, non-binding molecules does not interfere with quantification, which allows one to measure the concentration of the molecule of interest in a crude mixture. Here we apply this method to determining the dynamic binding capacity of affinity resins.     

Recovery from training: a brief review: brief review

Athletes spend a much greater proportion of their time recovering than they do in training. Yet, much attention has been given to training with very little investigation of recovery. The purpose of this review is to stimulate further research into this vital area of training. Recovery can be categorized in three terms: i) immediate recovery between exertions; ii) short-term recovery between repeats (e.g., between resistance sets or interval bouts); and iii) training recovery between workouts. The focus of this review is training recovery. Full training recovery is essential to optimal performance and improvement. This review includes an examination of extant research on recovery and a very brief review of some potential modalities and techniques for hastening recovery and the time course of recovery and responses to some treatments. Measures of recovery and practical considerations are discussed briefly. Much research is needed in this area, but there are obstacles to high quality research. Attention must be given to key issues in research on recovery, especially the individual response to recovery treatments.     

Responses of aerobic microbial communities and soil respiration to water-level drawdown in a northern boreal fen

On a global basis, peatlands are a major reserve of carbon (C). Hydrological changes can affect the decomposition processes in peatlands and in turn can alter their C balance. Since 1959, a groundwater extraction plant has generated a water-level gradient at our study site that has gradually changed part of the wet fen into a dry peatland forest. The average water-level drawdown of the gradient (from a pristine 9 cm to 26 cm in the dry end) is close to an estimate predicted by an increase in mean global temperature of 3°C. We studied the total microbial community of the aerobic surface peat in four locations along the gradient through phospholipid fatty acid and PCR-DGGE methods. Additionally, field measurements of soil respiration showed a threefold increase in the C-emission rate at the driest location compared with the wettest one, indicating enhanced decomposition. Also, both fungal and bacterial biomass increased in the drier locations. At the species level, the fungal community changed due to water-level drawdown whereas actinobacteria were less sensitive to drying. The majority of fungal sequences were similar to ectomycorrhizal (ECM) fungi, which dominated throughout the gradient. Our results indicate that ECM fungi might act as important facultative decomposers in organic-rich environments such as peatlands.     

Diagnosis and treatment of dementia: 5. Nonpharmacologic and pharmacologic therapy for mild to moderate dementia

Background

Practising physicians frequently seek advice on the most effective interventions for dementia. In this article, we provide practical guidance on nonpharmacologic and pharmacologic interventions for the management of mild to moderate dementia based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia.

Methods

We developed evidence-based guidelines using systematic literature searches, with specific criteria for the selection and quality assessment of articles, and a clear and transparent decision-making process. We selected articles published from January 1996 to December 2005 that dealt with the management of mild to moderate stages of Alzheimer disease and other forms of dementia. Recommendations based on the literature review were drafted and voted on. Consensus required 80% or more agreement by participants. Subsequent to the conference, we searched for additional articles published from January 2006 to April 2008 using the same major keywords and secondary search terms. We graded the strength of the evidence using the criteria of the Canadian Task Force on Preventive Health Care.

Results

We identified 1615 articles, of which 954 were selected for further study. From a synthesis of the evidence in these studies, we made 48 recommendations for the management of mild to moderate dementia (28) and dementia with a cerebrovascular component (8) as well as recommendations for addressing ethical issues (e.g., disclosure of the diagnosis) (12). The updated literature review did not change these recommendations. An exercise program is recommended for patients with mild to moderate dementia. Physicians should decide whether to prescribe a cholinesterase inhibitor on an individual basis, balancing anticipated benefits with the potential for harm. For mild mood and behavioural concerns, nonpharmacologic approaches should be considered first.

Interpretation

Although the available therapies for dementia can help with the management of symptoms, there is a need to develop more effective interventions.

Articles to date in this series

• Chertkow H. Diagnosis and treatment of dementia: Introduction. Introducing a series based on the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. CMAJ 2008;178:316-21.
• Patterson C, Feightner JW, Garcia A, et al. Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ 2008;178:548-56.
• Feldman HH, Jacova C, Robillard A, et al. Diagnosis and treatment of dementia: 2. Diagnosis. CMAJ 2008;178:825-36.
• Chertkow H, Massoud F, Nasreddine Z, et al. Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia. CMAJ 2008;178:1273-85.
• Hogan DB, Bailey P, Black S, et al. Diagnosis and treatment of dementia: 4. Approach to management of mild to moderate dementia. CMAJ 2008;179:787-93.

     

Validation of the MERIS products on large European lakes: Peipsi,Vänern and Vättern

The Medium Resolution Imaging Spectrometer (MERIS/Envisat) was launched in March 2002 for coastal zone monitoring. Preliminary data from MERIS show that its imagery of large lakes is superior to that of other common ocean colour sensors. The main objective of the present study is to evaluate the MERIS data on large European lakes, Vänern and Vättern in Sweden and Peipsi in Estonia/Russia. In these lakes, coloured dissolved organic matter (CDOM) can be a major contributor to the optical properties of the water. Another characteristic of the waters under investigation is the large temporal and spatial variability in the concentrations of chlorophyll (C _Chl) and suspended sediments (C _TSS). Potentially toxic cyanobacterial blooms occur in Lake Peipsi in late summer. We have compared the MERIS products from the latest reprocessing (finished in March 2006) with available in situ data. There is a reasonably good correlation between the MERIS algal_2 product and the measured C _chl over all three lakes, but no correlation was found for other optically active substances. A significant portion of the pixels (up to 90%) are flagged as invalid results after atmospheric correction.