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Alzheimer's disease as a defect of neuronal autotrophism: a hypothetical analogy with amateur radio operation.

Amyloid precursor protein appears to be a signaling protein that plays a role in neuronal autotrophism, indicating integrity of the nerve terminal and synapse. Analogous to amateur radio operation with a damaged antenna in which further attempts to improve signal propagation can result in damage to the radio equipment, abnormal signaling by the secreted amyloid precursor protein stimulates compensatory metabolic activity in the neuron that ultimately leads to paired helical filament formation (neurofibrillary tangles) and further neuronal dysfunction and death.

Alzheimer Disease↗

Molecular cloning, phylogenetic analysis and three-dimensional modeling of Cu,Zn superoxide dismutase (CnSOD1) from three varieties of Cryptococcus neoformans.

Cryptococcus neoformans (Cn), causal agent of fungal meningoencephalitis, has three varieties with variable host predilection. To explore mechanisms for these pathogenic differences, we have characterized Cu,Zn SOD gene (CnSOD1). A Saccharomyces cerevisiae sod1Delta mutant was complemented with Cn var. grubii yeast expression library. The complementing clone had an ORF of 462 bp and the deduced 154 aa sequence showed 61% identity with S. cerevisiae SOD1 and 53-65% with other eukaryotic SOD1s. Cn var. grubii CnSOD1 cDNA was used to clone corresponding cDNAs from var. neoformans and var. gattii. ORFs from three varieties revealed 20-29% differences in deduced aa (s) with a significant 6% non-synonymous aa substitution between Cn var. grubii and Cn var. gattii. Cosmid library screening and PCR cloning were used to obtain genomic SOD1, which was split by five introns with identical placements and a typical 5' splice junction sequence, GTNNGY. These introns also showed a large nt variation among the three Cn varieties. Phylogenetic analyses revealed CnSOD1 to be in a group distinct from other eukaryotic SOD1s and with a significant divergence of the var. grubii from var. gattii. The CnSOD1 -deduced protein was modeled based on the crystal structure of S. cerevisiae SOD1, which showed an excellent fit. Most of the non-synonymous aa substitutions occurred on the outside of the molecule and these may contribute to differences in antigenicity among the three varieties. Notably, Cn var. neoformans and var. gattii Cu,Zn SOD had three substitutions of glycine (Gly26, Gly92 and Gly123 for Asn26, Ser92 and Ser123) that may contribute to the observed lower thermostability of this enzyme vis-a-vis Cn var. grubii. This is the first nucleotide and structural comparison of a protein-encoding gene from the three Cn varieties, which may provide a framework for future studies on the role of Cu,Zn SOD in Cn pathogenesis.

Amino Acid Sequence↗

Parental understanding of basic infant nutrition: misinformed feeding choices.

To assess mothers' knowledge of good infant nutritional practices, a survey was conducted by the Institute of Pediatric Nutrition. The survey addressed issues related to breast-feeding, the use of iron-fortified formula, frequent spitting up, the introduction of cow's milk into the infant diet, and the nutritional value of fruit juice. Mothers who responded to the survey had difficulty identifying the most appropriate choices. This article presents the survey results and discusses the implications for health care providers who care for children and their families.

Adult↗

Violence prevention.

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Adolescent↗

Sun protection.

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Child↗

Activation and secretion of Serratia hemolysin.

The hemolysin of Serratia marcescens (ShlA) is secreted into the culture medium and forms small pores of a defined size in erythrocytes and in black lipid membranes. The protein is synthesized as an inactive precursor of 1608 residues which is translocated across the cytoplasmic membrane by the Sec-export system. In the absence of the outer membrane protein ShlB, the ShlA protein (designated ShlA*) stays in the periplasm and displays about 0.1% of the activity of the secreted form. Secretion of ShlA with the help of ShlB is accompanied by its conversion to the hemolytic form. A ShlA derivative consisting of the N-terminal 238 residues of ShlA is secreted by ShlB, showing that the secretion signal resides in the amino terminal part of ShlA. ShlA* can be activated in vitro by a cell lysate containing ShlB, the activated ShlA remains hemolytic upon removal of ShlB. The assumed covalent modification of ShlA* by ShlB occurs in the N-terminus of ShlA since an amino terminal fragment (M(r) 28,000) secreted by ShlB, and a trypsin fragment of ShlA (M(r) 15,000) are both able to convert ShlA* to a hemolytic protein. In contrast to the permanent modification of ShlA* by ShlB, ShlA activity achieved by complementation with the ShlA fragments is abolished upon removal of the fragments. Apparently, the N-terminal portion of ShlA contains the information for secretion through the outer membrane and for insertion into the erythrocyte membrane. This information is lacking in ShlA* formed in the absence of ShlB but contained in the ShlA fragments formed in the presence of ShlB. The latter bind to ShlA* and direct ShlA* into the erythrocyte membrane. The fragments themselves are too short to build pores. The HpmA hemolysin of Proteus mirabilis shows extensive homology to ShlA. In vitro activation of HpmA* by ShlB and complementation by the 28 kDa ShlA fragment indicates a common activation mechanism.

Amino Acid Sequence↗

The effect of short term confinement stress on binding characteristics of sex steroid binding protein (SBP) in female black bream (Acanthopagrus butcheri) and rainbow trout (Oncorhynchus mykiss).

The effect of short term confinement stress on sex steroid binding protein (SBP) binding characteristics was examined in female black bream (Acanthopagrus butcheri), and rainbow trout (Oncorhynchus mykiss). Black bream were sampled immediately after capture from the wild and again after 1, 6 or 24 h confinement. Rainbow trout were sampled before and after 5 h confinement. Confinement of black bream for 6 h after capture significantly reduced the binding capacity of SBP. Binding affinity also tended to be lower after confinement. There were no differences in binding affinity or capacity of black bream SBP after 1 or 24 h confinement, or rainbow trout SBP after 5 h confinement. Plasma from rainbow trout at 3 and 6 h after treatment with cortisol was compared to plasma from saline-injected controls. No significant differences in binding characteristics were detected, but there was a trend of decreased binding capacity in cortisol-injected fish compared to controls at 6 h post-injection. Relative binding studies indicated that plasma cortisol at concentrations 100x or more greater than plasma estradiol (E(2)) may displace E(2) from SBP in black bream, and act to reduce circulating levels of E(2) through increased clearance of free steroid. Physiological levels of cortisol did not displace E(2) from SBP in trout. The observed changes in SBP and the competition of physiological concentrations of cortisol for SBP binding sites may generate a component of the stress-induced falls in plasma levels of E(2) reported across a range of species.

Animals↗

Missed opportunities in the field: caring for clients with co-morbidity problems.

This discussion paper presents key issues associated with caring for people with concurrent alcohol or drug and mental health problems. By way of anecdotal stories and personal experiences, it draws attention to 'missed opportunities' for effective care of clients within a general hospital and community mental health service. As educators, inicians and students, we are concerned our own attempts to improve the care of these clients may have been less than successful due to various factors, and believe such information is important to share with the wider nursing profession. We hope the paper will stimulate interest amongst general, mental health and drug and alcohol nurses, and researchers and educators to better address the issue of alcohol, drug and mental health co-morbidity in our community.

Attitude of Health Personnel↗

Feasibility of a cognitive-behavioural group intervention for men experiencing psychological difficulties after myocardial infarction.

BACKGROUND: People experiencing psychological distress after a cardiac event may require special follow-up and targeted interventions in order to effectively decrease levels of distress. AIMS: Men who were judged to be experiencing poor emotional adjustment post-myocardial infarction (MI) were invited to a cognitive behaviour therapy group. The current study examines the attendance at such a group and the consequent feasibility of such interventions. METHOD: The content of the group aimed to help men deal with the uncomfortable psychosocial issues that had arisen since having a MI. RESULTS: Of the 26 men approached only 30% were interested in attending and only 11% actually completed the group. Two men who were committed to attending the group could not complete all the sessions, as heart bypass operations became available to them. CONCLUSION: Ways of involving men in interventions targeting psychological distress requires ongoing investigation.

Cognitive Behavioral Therapy↗

The effects of pulp mill effluent on the sex steroid binding protein in white sucker (Catostomus commersoni) and longnose sucker (C catostomus).

The objective of this study was to characterize the effects of pulp mill effluent on the properties of the sex steroid binding protein (SBP) in the plasma of white sucker (Catostomus commersoni) and longnose sucker (C. catostomus). SBPs which specifically bind estradiol and testosterone with high affinity (k(D) approximately 3 nM) and low capacity (B(max) approximately 73-81 nM) were identified in both species. Subsequent studies determined if the properties of the SBP in white sucker exposed to bleached kraft mill effluent (BKME) at Terrace Bay, ON, and in longnose sucker exposed to BKME at Grande Prairie, AB. differed from appropriate reference fish. There were no effects of BKME exposure on the binding affinity (k(D)) of the SBP in either species, but there was a significant increase in the binding capacity (B(max)) of longnose sucker SBP exposed to BKME. The livers of nai;ve white sucker exposed to effluent at Terrace Bay or a bleached sulfite/groundwood mill in Edmundston, NB, rapidly accumulated compounds of differing hydrophobicity that bound to both the white sucker and goldfish (Carassius auratus) SBP. Conversely, there was reduced accumulation of SBP ligands in the bile of effluent-exposed fish. We have demonstrated that constituents present within pulp mill effluent bind to both the white sucker and goldfish SBP, and that native species residing downstream of pulp mill effluents may experience modifications in the properties of their SBP.

Animals↗

Equivalence of information from single frequency v. bioimpedance spectroscopy in bodybuilders.

In bioelectrical impedance spectroscopy (BIS), it is assumed that the current path is only extracellular at the lowest frequencies and that it is both extra- and intracellular at the highest frequencies. We tested validity of BIS assumptions in bodybuilders who have an increased intracellular volume due to hypertrophy of muscle fibres. The study was observational cross-sectional in a study group of thirty professional bodybuilders compared with thirty control subjects. Resistance (R) and reactance (Xc) vector components fitting the Cole's arc with BIS (SFB3 analyser) were compared with components at 50 kHz frequency. The average Cole's arc in bodybuilders was significantly smaller and shifted to the left in the R-Xc plane (both R and Xc values were smaller at any individual frequency). The ratio of Xc at 5 kHz and Xc at the characteristic frequency was 70% in bodybuilders and 64% in control subjects, indicating a huge intracellular flow of the electric current at low frequencies in both groups (expected ratio close to 0 if the current path was extracellular). As a consequence of a common path, the correlation coefficient between R values at 50 kHz and at other frequencies (from 0 to infinity) was 0.94 to 1.00. The correlation between total body water estimated with BIS or with R at 50 kHz was 0.98. Hence, there was equivalence between information provided by the vector components R and Xc at 50 kHz and that provided by 496 correlated vectors that were measured with BIS.

Adolescent↗

Noise levels and exposure patterns to do-it-yourself power tools.

The noise levels produced by a variety of do-it-yourself power tools were measured in a real-life situation. Most of the devices tested produced noise of 100 dB(A) or greater at the user's ear. A questionnaire was issued to 100 males who used these devices. The vast majority used the devices infrequently and therefore are unlikely to be directly at risk of hearing damage. A group of users who may be more at risk from using power tools in the home are those who are, or have been exposed to occupational noise.

Adolescent↗

Carbon use, nitrogen use, and isotopic fractionation of ectomycorrhizal and saprotrophic fungi in natural abundance and 13C-labelled cultures.

Stable isotopes in fruit bodies from field studies have been used to infer ectomycorrhizal or saprotrophic status and to understand carbon and nitrogen use, but few controlled culture studies have correlated source and fungal isotopic patterns. Here, we measured natural abundances of 15N and 13C in ten strains of ectomycorrhizal fungi and seven strains of saprotrophic fungi grown on agar with three different primary carbon sources: glucose, glucose plus malt extract, and potato dextrose agar. Eight fungal strains were also grown using position-specific, 13C-labelled glucose (C-1 through C-6 labelled). Most fungi resembled nitrogen sources in delta 15N, suggesting that growth on agar media minimizes isotopic fractionation on uptake compared to growth on liquid media, and that in general saprotrophic and mycorrhizal fungi process nitrogen similarly. Saprotrophic fungi were more depleted in 13C than ectomycorrhizal fungi on all media, presumably because of assimilation of 13C-depleted, agar-derived carbon. Results on 13C-enriched glucose indicated that saprotrophic fungi obtained up to 45 % of their carbon from the agar substrate. Fungi generally incorporated the individual carbon atoms of glucose in the order, C-4 < C-1 < C-2, C-3, C-5 < C-6, ranging from a mean of 9 % for the C-4 atom to 21 % for the C-6 atom. Based on these incorporation patterns and intramolecular 13C patterns within glucose, differential incorporation of carbon atoms within glucose among fungal taxa contributed less than 1% to isotopic differences among taxa, whereas isotopic fractionation among taxa during metabolism varied up to 4%. Parallel studies of 13C-enriched and natural abundance substrates were crucial to interpreting our results.

Carbon↗