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PubMed2004

Self-assembly of the cytoskeletal glial fibrillary acidic protein is inhibited by an isoform-specific C terminus.

The predominant isoform of glial fibrillary acidic protein (GFAP), GFAPalpha, is the characteristic building block of the cytoskeletal intermediate filaments in astrocytes. Isoform GFAPepsilon, produced by alternative splicing of the GFAP gene, includes a new tail domain that confers a presenilin binding capacity. We here show that the GFAPepsilon tail prevents GFAPepsilon homodimerization and homomeric filament formation, whereas the ability to form heterodimers and filaments with GFAPalpha is retained. Furthermore, GFAPepsilon shows decreased affinity for several GFAPalpha-interacting proteins. A GFAPepsilon tail mutation that results in gain of GFAPepsilon dimerization and filament formation abolishes presenilin binding. This mutation also abolishes interaction between the tail and the coiled-coil domain of GFAPepsilon. Together, this indicates that direct interaction between the coiled-coil and tail domains may serve as an inhibitory mechanism for homomeric dimerization and filament formation. We propose that the GFAPepsilon isoform represents a new functionally distinct component of GFAP intermediate filaments.

Amino Acid Sequence↗
PubMed2006

Molecularly imprinted polymers for the clean-up of a basic drug from environmental and biological samples.

A molecularly imprinted polymer (MIP) was synthesized and evaluated to selectively extract an alpha-blocker, i.e. alfuzosin, from human plasma. The synthesis of the MIP was performed in dichloromethane with methacrylic acid as monomer and the target drug as template. A first series of experiments was carried out in dichloromethane to estimate the potential of the MIP in its specific recognition medium, i.e. dichloromethane, by developing a selective procedure and by measuring the capacity of the sorbent. An optimized procedure was developed for the selective extraction of alfuzosin with a recovery close to 100% in this medium and a specific capacity of 1.3 micromol g(-1) of MIP was measured. A study in aqueous media was also carried out by a comprehensive approach of the retention mechanism in order to build a selective procedure of extraction. The effects of the amount and of the charge of cations were studied and an optimal pH value was defined to limit matrix effects. Then, the alfuzosin MIP was then directly used to selectively extract the target drug from human plasma with an extraction recovery of 60%. Lastly, a soil was extracted by a pressurized solvent and the resulting extract was cleaned up on the MIP, showing the possibility to use this selective sorbent for the sample treatment of various complex matrices.

Adrenergic alpha-Antagonists↗
PubMed2001

Respiratory and circulatory compensation to hypoxia in crustaceans.

Crustaceans are often tolerant of hypoxic exposure and many regulate O(2) consumption at low ambient O(2). In acute hypoxia, most increase branchial water flow, and many also increase branchial haemolymph flow, both by an increase in cardiac output and by shunting flow away from the viscera. The O(2)-binding affinity of crustacean O(2) carriers increases in hypoxic conditions, as a result of hyperventilation induced alkalosis. In chronic hypoxic exposure some crustaceans do not sustain high ventilatory pumping levels but increased effectiveness of O(2)-uptake across the gills is maintained as a result of the build up of metabolites such as lactate and urate which also function to increase the haemocyanin O(2)-binding affinity. Chronic exposure to hypoxia also may increase O(2)-binding capacity and promote the synthesis of new high O(2)-affinity carrier molecules. Exposure to untenable rates or levels of O(2) depletion causes many decapodan crustaceans to surface and ventilate the gills with air. Burrowing crayfish provide an example of animals, which excel in all these mechanisms. Control mechanisms involved in compensatory responses to hypoxia are discussed.

Animals↗
PubMed1999

Distortion product otoacoustic emissions and outer hair cell defects in the hyt/hyt mutant mouse.

Thyroid hormone plays an important role in hearing development. Hereditary hypothyroidism is frequently associated with sensorineural hearing loss as identified in both animal models and human patients. Building upon our original demonstration of congenital deafness and hair cell abnormality in a hyt/hyt mouse model which carries an autosomal recessive mutation causing hereditary hypothyroidism, we investigated the functional capacity of the outer hair cell (OHC) system in these animals using distortion product otoacoustic emissions (DPOAEs). In particular, the amplitude and detection features of DPOAEs were correlated with measures of the auditory brainstem response (ABR) as well as the cellular structure and ultrastructure of the organ of Corti. Input-output (I/O) functions for the 2f(2)-f(1) DPOAEs were obtained for frequencies from 2 to 18 kHz. The thresholds were significantly higher and amplitudes were significantly lower in the homozygous mice (hyt/hyt) than in both heterozygous mice (hyt/+) and wild-type controls at DPOAE frequencies recorded above 6 kHz. Hearing thresholds were significantly elevated in the mutant compared to control mice. In addition, morphological studies revealed consistent inner ear defects in hyt/hyt animals including distortion of the tectorial membrane, dysplasia of the tunnel of Corti and distinct OHC abnormalities. The most striking histopathological finding was a contiguous membrane along the apices of all of the OHC stereocilia. Such ultrastructural changes in the stereocilia of the OHC may limit the deflection of the stereocilia and therefore affect an active cochlear function that produces otoacoustic emissions as well as cause a failure to evoke the normal action potentials in the auditory nerve. From both functional and morphologic evaluations, it was concluded that the OHC system is the most susceptible to the developmental effects of congenital hypothyroidism in the hyt/hyt mouse. The normal OHCs with well-developed ciliary bundles are crucial to maintain the activity of biological mechanisms within the cochlea.

Animals↗
PubMed1993

Health technologies for the developing world. Promoting self-reliance through improving local procurement and manufacturing capabilities.

To reduce their dependency on donors or the international currency costs of essential health care products, developing countries are building or improving capability for local manufacturing or competitive international procurement. Through long-term strategic planning, public/private partnerships, collaboration with firms in industrialized nations, and farsighted donor policies, the capacity for alternative supply can be increased in stages from importation through local processing and packaging to full production and multiproduct enterprises.

Cost Control↗
PubMed1997

The growth rate control in Escherichia coli at near to maximum growth rates: the A-stat approach.

The growth characteristics of Escherichia coli K-12 in the continuous culture with a smooth increase in the dilution rate (A-stat) of various carbon sources (glucose, acetate, succinate, glycerol, lactate, acetate + succinate, casamino, acids + glucose) were studied. For all substrates studied the maximum value of specific respiration rate, QO2, remained between 14-18 mmol O2 h-1 g dwt-1 and the maximum growth rate varied from 0.22 h-1 on acetate to 0.77 h-1 on glucose + casamino acids. After the respiratory capacity of the cells was exhausted at growth rates mu > mu crit, the growth yield YXO2, increased slightly when the dilution rate increased. The maximum growth rate of Escherichia coli K12 was dependent on growth yield, respiratory capacity and glycolytic capacity of the strain. Analysis of the cultivation data using a stoichiometric flux model indicated that ATP synthesis in E. coli exceeds by two-fold that (theoretically) required to build up biomass. The experimental value of mATP < 4 mmol ATP h-1 g dwt-1 determined from A-stat cultivation data was low compared with the calculated 'unproductive hydrolysis' of ATP (64-103 mmole ATP g dwt-1).

Acetates↗
PubMed2004

Demography of the cereal rust mite Abacarus hystrix (Acari: Eriophyoidea) on quack grass.

Demography parameters of the cereal rust mite Abacarus hystrix (Nalepa) on quack grass were studied to investigate its potential capacity of population increase in conditions of initially low density. The experiment was maintained under laboratory conditions at a constant temperature of 19.5-20.5 degrees C and 94 +/- 1% RH. Life-history data were used to calculate duration of developmental stages, survival of adults and rates of population increase. A new method of estimation of age-dependent fecundity is proposed. On average, eggs required 7.98 (n = 33, 95% CI: 7.68-8.21) days to develop into adults. Life expectancy of females was longer than that of males (9.72 and 5.41 days, respectively). The mean sex ratio, expressed as the proportion of females, was 0.80 (n = 122, CI: 0.71-0.86). The reproductive output for females was age-dependent and daily egg production reached a peak (3.83 eggs/day, CI: 2.50-5.15) on the 5th day, and then decreased steeply. The net reproductive rate (R0) was 10.12 female progeny per female per generation, the generation time (T) was 11.31 days, the intrinsic rate of increase (r) was 0.20 female progeny per female per day, and the finite rate of increase (lambda) was 1.23 female progeny per day. These estimates showed that A. hystrix has a great potential capacity for rapid population increase when colonising new hosts and its density is low. Therefore, we conclude that the population of the cereal rust mite on quack grass may rapidly build up to very high densities and can be a reservoir population, which may easily disperse and infest other, including cultivated, grasses.

Animals↗
PubMed2005

Mainstreaming HIV/AIDS in development sectors: Have we learnt the lessons from gender mainstreaming?

Drawing on an international literature review, two international workshops and primary qualitative research in Uganda this paper reviews experiences of mainstreaming HIV/AIDS in development sectors (such as education, health and agriculture) in developing countries. The extent to which HIV/AIDS mainstreaming strategies and associated challenges are similar to or different from those of mainstreaming gender in the health sector is also explored. The paper details the rationale for HIV/AIDS mainstreaming through illustrating the wide reaching effects of the pandemic. Despite the increasing interest in mainstreaming HIV/AIDS there is little clarity on what it actually means in theory or practice. This paper presents a working definition of HIV/AIDS mainstreaming. It is argued that all too often processes of 'mainstreaming' emerge as too narrow and reductionist to be effective. The paper then considers four key challenges for mainstreaming HIV/AIDS and explores how and to what extent they have also been faced in gender mainstreaming and what can be learnt from these experiences. These are: (1) the limited evidence base upon which to build mainstreaming strategies in different country contexts; (2) the role of donors in mainstreaming and implications for sustainability; (3) who should take responsibility for mainstreaming; and (4) how to develop capacity for mainstreaming. The conclusion argues for more joined up thinking and sustainable approaches to mainstreaming both HIV/AIDS and gender.

Female↗
PubMed2004

Effects of matrix heterogeneity on animal dispersal: from individual behavior to metapopulation-level parameters.

Mounting theoretical and empirical evidence shows that matrix heterogeneity may have contrasting effects on metapopulation dynamics by contributing to patch isolation in nontrivial ways. We analyze the movement properties during interpatch dispersal in a metapopulation of Iberian lynx (Lynx pardinus). On a daily temporal scale, lynx habitat selection defines two types of matrix habitats where individuals may move: open and dispersal habitats (avoided and used as available, respectively). There was a strong and complex impact of matrix heterogeneity on movement properties at several temporal scales (hourly and daily radiolocations and the entire dispersal event). We use the movement properties on the hourly temporal scale to build a simulation model to reconstruct individual dispersal events. The two most important parameters affecting model predictions at both the individual (daily) and metapopulation scales were related to the movement capacity (number of movement steps per day and autocorrelation in dispersal habitat) followed by the parameters representing the habitat selection in the matrix. The model adequately reproduced field estimates of population-level parameters (e.g., interpatch connectivity, maximum and final dispersal distances), and its performance was clearly improved when including the effect of matrix heterogeneity on movement properties. To assume there is a homogeneous matrix results in large errors in the estimate of interpatch connectivity, especially for close patches separated by open habitat or corridors of dispersal habitat, showing how important it is to consider matrix heterogeneity when it is present. Movement properties affect the interaction of dispersing individuals with the landscape and can be used as a mechanistic representation of dispersal at the metapopulation level. This is so when the effect of matrix heterogeneity on movement properties is evaluated under biologically meaningful spatial and temporal scales.

Animal Migration↗
PubMed1991

Effects of dietary supplementation on work performance in Gambian laborers.

The effect of food supplementation on productivity of Gambian subsistence farmers was studied during a natural food shortage induced by the annual hungry season. Sixteen men in two groups matched for weight, height, hemoglobin, and physical-work capacity followed a crossover protocol with 6-wk supplementation and control periods. Productivity was assessed over the final 3 wk of each period by quantifying piece-rate-paid road building. Supplementation comprised an ad libitum supply of highly palatable energy-dense food provided three times daily. Outcome variables were total loads transported, loads per working hour, time per load, total energy expenditure assessed by doubly labeled water and heart-rate monitoring, postwork activity, and anthropometry. Body weight decreased during control periods, indicating a real energy deficit, and increased during supplementation in both groups. Supplementation had no significant impact on productivity variables. Energy-deficient men can maintain maximal productivity over short periods if sufficiently motivated but at the expense of body weight.

Adult↗
PubMedDate not supplied

Testing for neutral-to-ground connections in new construction.

A study was performed to seek out inadvertent connections between neutral and ground in the power distribution system of a newly constructed hospital, prior to occupancy. Such connections are not only violations of code but could cause medical device problems. Ground wires are not intended to carry load currents except during faults. When currents do flow in grounds, medical device chassis voltages are elevated and some devices may respond unpredictably. Suitable acceptance testing is not commonly done. In this study, a simple test method was developed that helped reveal and correct many neutral-ground misconnections. The authors advocate incorporating such a test into building construction contract specifications.

Electric Power Supplies↗
PubMedDate not supplied

Management development is imperative in small/rural hospitals.

Management development is important for all health care institutions, but for small and rural hospitals it could be the pivot point for survival in the 1980s. The program described here concentrates not only on developing managers' skills but also on building a team approach to hospital management.

Administrative Personnel↗
PubMed2002

Building partnerships to respond to HIV/AIDS: non-governmental organizations and universities.

BACKGROUND: In the second decade of the AIDS epidemic in Brazil, public sector and non-governmental organization (NGO) initiatives multiplied, fostered by state AIDS Control Programmes. A growing gap between capacity and a need for programme evaluation and the dissemination of findings from experience in the field, combined with the failure of traditional training approaches to bridge this gap adequately, inspired this non-degree research training programme at a major Brazilian university. OBJECTIVES: To train health professionals and activists working with HIV/AIDS prevention and services to evaluate and disseminate their experiences, and to enable them to multiply this training in their organizations, working in a collaborative process with graduate students and senior researchers. PROCEDURES: As part of a 9-month research methods course, 52 representatives from NGO and public health services produced research protocols that were reviewed and strengthened through a formal peer review process. Eleven protocols judged to be the best received funding and close mentorship over the next 21 months for their implementation, analysis, and dissemination. LESSONS LEARNED: Participants increased their ability to master and review critically the AIDS literature, to conduct a research protocol and to disseminate the results of their studies. After completion of the 30-month process, many participants were able to present their findings at scientific conferences or publish their results in peer-reviewed scientific journals. This model of close NGO-university successful collaboration may inspire other models of research training for those in the front-lines of the fight against the epidemic.

Acquired Immunodeficiency Syndrome↗