Participation of kinin receptors on memory impairment after chronic infusion of human amyloid-beta 1-40 peptide in mice

Chronic infusion of human amyloid-beta 1-40 (A beta) in the lateral ventricle (LV) of rats is associated with memory impairment and increase of kinin receptors in cortical and hippocampal areas. Deletion of kinin B1 or B2 receptors abolished memory impairment caused by an acute single injection of A beta in the LV. As brain tissue and kinin receptors could unlikely react to acute or chronic administration of a similar quantity of A beta, we evaluated the participation of B1 or B2 receptors in memory impairment after chronic infusion of A beta. Male C57BI/6 J (wt), knock-out B1 (koB1) or B2 (koB2) mice (12 weeks of age) previously trained in a two-way shuttle-box and achieving conditioned avoidance responses (CAR, % of 50 trials) were infused with AB (550 pmol, 0.12 mu L/h, 28 days) or vehicle in the LV using a mini-osmotic pump. They were tested before the surgery (TO), 7 and 35 days after the infusion started (T7; T35). In T0, no difference was observed between CAR of the control (Cwt = 59.7 +/- 6.7%; CkoB1 = 46.7 +/- 4.0%; CkoB2 = 64.4 +/- 5.8%) and A beta (A beta wt = 66.0 +/- 3.0%; A beta koB1 = 66.8 +/- 8.2%; A beta koB2 = 58.7 +/- 5.9%) groups. In T7, A beta koB2 showed a significant decrease in CAR (41.0 +/- 8.6%) compared to the control-koB2 (72.8 +/- 2.2%, P <0.05). In T35, a significant decrease (P <0.05) was observed in A beta wt (40.7 +/- 3.3%) and A beta koB2 (41.2 +/- 10.7%) but not in the A beta koB1 (64.0 +/- 14.0%) compared to their control groups. No changes were observed in the controls at T35. We suggest that in chronic infusion of BA, B1 receptors could playan important role in the neurodegenerative process. Conversely, the premature memory impairment of koB2 suggests that it may be a protective factor. (C) 2009 Elsevier Ltd. All rights reserved.

The accuracy of the Clock Drawing Test compared to that of standard screening tests for Alzheimer`s disease: results from a study of Brazilian elderly with heterogeneous educational backgrounds

Background: Although the Clock Drawing Test (CDT) is the second most used test in the world for the screening of dementia, there is still debate over its sensitivity specificity, application and interpretation in dementia diagnosis. This study has three main aims: to evaluate the sensitivity and specificity of the CDT in a sample composed of older adults with Alzheimer`s disease (AD) and normal controls; to compare CDT accuracy to the that of the Mini-mental State Examination (MMSE) and the Cambridge Cognitive Examination (CAMCOG), and to test whether the association of the MMSE with the CDT leads to higher or comparable accuracy as that reported for the CAMCOG. Methods: Cross-sectional assessment was carried out for 121 AD and 99 elderly controls with heterogeneous educational levels from a geriatric outpatient clinic who completed the Cambridge Examination for Mental Disorder of the Elderly (CAMDEX). The CDT was evaluated according to the Shulman, Mendez and Sunderland scales. Results: The CDT showed high sensitivity and specificity. There were significant correlations between the CDT and the MMSE (0.700-0.730; p < 0.001) and between the CDT and the CAMCOG (0.753-0.779; p < 0.001). The combination of the CDT with the MMSE improved sensitivity and specificity (SE = 89.2-90%; SP = 71.7-79.8%). Subgroup analysis indicated that for elderly people with lower education, sensitivity and specificity were both adequate and high. Conclusions: The CDT is a robust screening test when compared with the MMSE or the CAMCOG, independent of the scale used for its interpretation. The combination with the MMSE improves its performance significantly, becoming equivalent to the CAMCOG.

Temporomandibular Disorder in Brazilian Patients: A Preliminary Study

The objective of the current study was to evaluate disease-related beliefs, adherence to treatment, quality of life, coping strategies and cognitive status in a group of Brazilian patients with Temporomandibular Disorder (TMD). Thirty patients were evaluated with a semi-directed interview, the Coping Strategies Inventory, and a Mini-Mental State Examination. Although half (50%) of the patients had known their diagnosis long term, 40% of the sample were not correctly following proposed treatment. All patients had a similar pattern of pain behavior related to TMD, while disease-related beliefs, quality of life and coping strategies were variable. Expectations about treatment also had significant association with treatment adherence. The findings of this study suggest that a more thorough understanding of individual differences in TMD is warranted.

Stress and coping in older people with Alzheimer`s disease

To investigate stress intensity and coping style in older people with mild Alzheimer`s disease. The potential risk assessment of a stress event and the devising of coping strategies are dependent on cognitive function. Although older individuals with Alzheimer`s disease present significant cognitive impairment, little is known about how these individuals experience stress events and select coping strategies in stress situations. Survey. A convenient sample of 30 cognitively healthy older people and 30 individuals with mild Alzheimer`s disease were given an assessment battery of stress indicators (Symptom Stress List, Cornell Scale for Depression in Dementia, State-Trait Anxiety Inventory), coping style (Jalowiec Coping Scale) and cognitive performance (mini-mental state exam) were applied in both groups. Statistical analysis of the data employed the Mann-Whitney test to compare medians of stress indicators and coping style, Fischer`s exact test to compare proportions when expected frequencies were lower than five, and Spearman`s correlation coefficient to verify correlation between coping style and cognitive performance. Both groups suffered from the same stress intensity (p = 0.254). Regarding coping styles, although differences were not statistically significant (p = 0.124), emotion-oriented coping was predominant in the patients with Alzheimer`s disease. However, those individuals displaying better cognitive performance in the Alzheimer`s disease group had selected coping strategies focused on problem solving (p = 0.0074). Despite a tendency for older people with Alzheimer`s disease to select escape strategies and emotional control, rather than attempting to resolve or lesser the consequences arising from a problem, coping ultimately depends on cognitive performance of the individual. The findings of this study provide information and data to assist planning of appropriate support care for individuals with Alzheimer`s disease who experience stress situations, based on their cognitive performance.

Cognitive impairment in cancer pain patients receiving opioids

This study aimed to compare cognitive function of cancer pain patients being given opioids during their cancer treatment (n = 14) with that of patients receiving treatment without opioids (n = 12). Correlations between cognitive function, pain intensity, and opioid dose were analyzed. Patients were assessed 3 times in a I-month period, using the Trail-Making Test, Mini-Mental State Examination, Digit Span, and Brief Cognitive Screening Battery. Opioid use was not associated with clear cognitive impairment. Patients being treated without opioids did perform better in the Digit Span Test reverse-order test (P = .029) and the clock drawing test (P = .023), but the differences arose in just I assessment in each case. Pain intensity correlated negatively with scores in the Mini-Mental State Examination (P = .001) and some Brief Cognitive Screening Battery tests (incidental recall, immediate recall, and late recall; P <= .042) in the group receiving opioids. Opioid dose did not correlate with any of the measures of cognitive performance. However, the patients with the worst performance scores were those with more severe pain. Further studies are needed to clearly distinguish between the effects of opioids versus the effects of pain.

Relationship Between Cortisol Levels and Memory Performance may be Modulated by the Presence or Absence of Cognitive Impairment: Evidence from Healthy Elderly, Mild Cognitive Impairment and Alzheimer`s Disease Subjects

An inverted U-shape function between cortisol levels and memory performance has been reported in studies on both young animals and humans. Yet little is known about this relationship in normal aging or in older subjects with cognitive impairment. This issue is particularly significant since increased levels of cortisol have been reported in Alzheimer`s disease (AD). The present study examined the association between cortisol levels and visual memory performance in healthy subjects as well as in individuals presenting mild cognitive impairment (MCI) or AD. Salivary cortisol was measured in 40 healthy elderly subjects, 31 individuals with amnestic MCI, and 40 subjects with mild probable AD. Memory performance was evaluated using the Brief Cognitive Screening Battery. Higher cortisol levels were associated with better memory performance in healthy elderly (p = 0.005), while higher cortisol levels were correlated with poorer memory performance in MCI subjects (p = 0.011). No correlation between cortisol and memory was found in the AD group (p > 0.05). These results suggest that the relationship between cortisol levels and memory performance in the aging process could vary according to the presence or absence of cognitive impairment.

Assessment of Depressive Symptoms and Cognitive Impairment in Elders From Rural Areas of the Brazilian State of Rio Grande do Sul

The main objective of this study was to examine the relationships among demographic characteristics, depressive symptoms, and cognitive impairment in oldest-old elders from rural areas of the Brazilian State of Rio Grande do Sul. A cross-sectional, descriptive correlational design was used to conduct the study. 137 Brazilian elders age 80 years or over. A target population data form, a county data form, a demographic questionnaire, the Mini-Mental State Examination, and the Depressive Cognition Scale were used to collect the data. A significant difference was found between males and females in regard to cognitive impairment. In addition, educational level and depressive symptoms were correlated with cognitive impairment. Depressive symptoms were a weak but significant predictor of cognitive impairment after controlling for the effect of age, gender, and educational level of the oldest-old elders. The findings need to be interpreted cautiously since the sample scored above the cutoff points for cognitive impairment, and had low scores on depressive symptoms. Despite several limitations, findings from this study can be a foundation for further studies, and well-designed correlational or experimental approaches, are warranted.

FtsH2 and FtsH5: two homologous subunits use different integration mechanisms leading to the same thylakoid multimeric complex

P>The Arabidopsis thylakoid FtsH protease complex is composed of FtsH1/FtsH5 (type A) and FtsH2/FtsH8 (type B) subunits. Type A and type B subunits display a high degree of sequence identity throughout their mature domains, but no similarity in their amino-terminal targeting peptide regions. In chloroplast import assays, FtsH2 and FtsH5 were imported and subsequently integrated into thylakoids by a two-step processing mechanism that resulted in an amino-proximal lumenal domain, a single transmembrane anchor, and a carboxyl proximal stromal domain. FtsH2 integration into washed thylakoids was entirely dependent on the proton gradient, whereas FtsH5 integration was dependent on NTPs, suggesting their integration by Tat and Sec pathways, respectively. This finding was corroborated by in organello competition and by antibody inhibition experiments. A series of constructs were made in order to understand the molecular basis for different integration pathways. The amino proximal domains through the transmembrane anchors were sufficient for proper integration as demonstrated with carboxyl-truncated versions of FtsH2 and FtsH5. The mature FtsH2 protein was found to be incompatible with the Sec machinery as determined with targeting peptide-swapping experiments. Incompatibility does not appear to be determined by any specific element in the FtsH2 domain as no single domain was incompatible with Sec transport. This suggests an incompatible structure that requires the intact FtsH2. That the highly homologous type A and type B subunits of the same multimeric complex use different integration pathways is a striking example of the notion that membrane insertion pathways have evolved to accommodate structural features of their respective substrates.

Influence of ammonium sulphate feeding time on fed-batch Arthrospira (Spirulina) platensis cultivation and biomass composition with and without pH control

Previous work demonstrated that a mixture of NH(4)Cl and KNO(3) as nitrogen source was beneficial to fed-batch Arthrospira (Spirulina) platensis cultivation, in terms of either lower costs or higher cell concentration. On the basis of those results, this study focused on the use of a cheaper nitrogen source mixture, namely (NH(4))(2)SO(4) plus NaNO(3), varying the ammonium feeding time (T = 7-15 days), either controlling the pH by CO(2) addition or not. A. platensis was cultivated in mini-tanks at 30 degrees C, 156 mu mol photons m(-2) s(-1), and starting cell concentration of 400 mg L(-1), on a modified Schlosser medium. T = 13 days under pH control were selected as optimum conditions, ensuring the best results in terms of biomass production (maximum cell concentration of 2911 mg L(-1), cell productivity of 179 mg L(-1) d(-1) and specific growth rate of 0.77 d(-1)) and satisfactory protein and lipid contents (around 30% each). (C) 2011 Elsevier Ltd. All rights reserved.

MHCPEP, a database of MHC-binding peptides: update 1997

MHCPEP (http://wehih.wehi.edu.au/mhcpep/) is a curated database comprising over 13 000 peptide sequences known to bind MHC molecules, Entries are compiled from published reports as well as from direct submissions of experimental data, Each entry contains the peptide sequence, its MHC specificity and where available, experimental method, observed activity, binding affinity, source protein and anchor positions, as well as publication references, The present format of the database allows text string matching searches but can easily be converted for use in conjunction with sequence analysis packages. The database can be accessed via Internet using WWW or FTP.

Prediction of MHC class II-binding peptides using an evolutionary algorithm and artificial neural network

Motivation: Prediction methods for identifying binding peptides could minimize the number of peptides required to be synthesized and assayed, and thereby facilitate the identification of potential T-cell epitopes. We developed a bioinformatic method for the prediction of peptide binding to MHC class II molecules. Results: Experimental binding data and expert knowledge of anchor positions and binding motifs were combined with an evolutionary algorithm (EA) and an artificial neural network (ANN): binding data extraction --> peptide alignment --> ANN training and classification. This method, termed PERUN, was implemented for the prediction of peptides that bind to HLA-DR4(B1*0401). The respective positive predictive values of PERUN predictions of high-, moderate-, low- and zero-affinity binder-a were assessed as 0.8, 0.7, 0.5 and 0.8 by cross-validation, and 1.0, 0.8, 0.3 and 0.7 by experimental binding. This illustrates the synergy between experimentation and computer modeling, and its application to the identification of potential immunotheraaeutic peptides.

Anatomy of the mouthparts and digestive tract during feeding in larvae of the parasitoid wasp Trichogramma australicum Girault (Hymenoptera : Trichogrammatidae)

To aid in the development of artificial diets for mass rearing parasitioids, we investigated the anatomical changes in the digestive tract during feeding behaviour of larval Trichogramma australicum (Hymenoptera: Trichogrammatidae). Larvae begin to feed immediately upon eclosion and feed continuously for 4 h until replete. Feeding is characterised by rhythmic muscle contractions (ca 1 per s) of the pharynx. Contractions of the pharyngeal dilator muscles lift the roof of the lobe-shaped pharynx away from the floor of the chamber, opening the mouth and pumping food into the pharyngeal cavity. Another muscle contraction occurs about 0.5 s later, forcing the bolus of food through the oesophagus and into the midgut. The junction of fore- and midgut is marked by a cardiac valve. The midgut occupies most of the body cavity and is lined with highly vacuolated, flattened cells and a dispersed layer of muscle cells. In the centre of the midgut, food has the appearance of host egg contents. Food near the midgut epithelial cells has a finer, more homogeneous appearance. This change in the physical properties of the gut contents is indicative of the digestion process. In the prepupa, where digestion is complete, the entire gut contents have this appearance. After eclosion, the vitelline membrane remains attached to the posterior end of the larva. We believe this attachment to be adaptive in two ways: (1) to anchor the larva against the movements of its anterior portion, thereby increasing the efficiency of foraging within the egg, and (2) to prevent a free-floating membrane from clogging the mouthparts during ingestion. 1998 Elsevier Science Ltd. All rights reserved.

The relationship between hetero-oligomer formation and function of the topological specificity domain of the Escherichia coli MinE protein

MinE is an oligomeric protein that, in conjunction with other Min proteins, is required for the proper placement of the cell division site of Escherichia coli. We have examined the self-association properties of MinE by analytical ultracentrifugation and by studies of hetero-oligomer formation in non-denaturing polyacrylamide gets. The self-association properties of purified MinE predict that cytoplasmic MinE is likely to exist as a mixture of monomers and dimers. Consistent with this prediction, the C-terminal MinE(22-88) fragment forms hetero-oligomers with MinE(+) when the proteins are co-expressed. In contrast, the MinE(36-88) fragment does not form MinE(+)/MinE(36-88) hetero-oligomers, although MinE36-88 affects the topological specificity of septum placement as shown by its ability to induce minicell formation when co-expressed with MinE(+) in wild-type cells. Therefore, hetero-oligomer formation is not necessary for the induction of mini-celling by expression of MinE(36-88) in wild-type cells. The interference with normal septal placement is ascribed to competition between MinE(36-88),nd the corresponding domain in the complete MinE protein for a component required for the topological specificity of septal placement.

A H-1 MRS study of probable Alzheimer's disease and normal aging: Implications for longitudinal monitoring of dementia progression

In order to evaluate the capability of H-1 MRS to monitor longitudinal changes in subjects with probable Alzheimer's disease (AD), the temporal stability of the metabolite measures N-acetylaspartate and N-acetylas-partylglutamate (NA), total Creatine (Cr), myo-Inositol (mI), total Choline (Chol), NA/Cr, mI/Cr, Chol/Cr and NA/mI were investigated in a cohort of normal older adults. Only the metabolite measures NA, mi, Cr, NA/Cr, mI/Cr, and NA/mI were found to be stable after a mean interval of 260 days. Relative and absolute metabolite measures from a cohort of patients with probable AD were subsequently compared with data from a sample of normal older adult control subjects, and correlated with mental status and the degree of atrophy in the localized voxel. Concentrations of NA, NA/Cr, and NA/mI were significantly reduced in the AD group with concomitant significant increases in mi and mI/Cr. There were no differences between the two groups in measures of Cr, Chol, or Chol/Cr. Significant correlations between mental status as measured by the Mini-Mental State Examination and NA/mI, mI/Cr and NA were found. These metabolite measures were also significantly correlated with the extent of atrophy (as measured by CSF and GM composition) in the spectroscopy voxel. (C) 1999 Elsevier Science Inc.

Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins

Retroviral entry into cells depends on envelope glycoproteins, whereby receptor binding to the surface-exposed subunit triggers membrane fusion by the transmembrane protein (TM) subunit. We determined the crystal structure at 2.5-Angstrom resolution of the ectodomain of gp21, the TM from human T cell leukemia virus type 1. The gp21 fragment was crystallized as a maltose-binding protein chimera, and the maltose-binding protein domain was used to solve the initial phases by the method of molecular replacement. The structure of gp21 comprises an N-terminal trimeric coiled coil, an adjacent disulfide-bonded loop that stabilizes a chain reversal, and a C-terminal sequence structurally distinct from HIV type 1/simian immunodeficiency virus gp41 that packs against the coil in an extended antiparallel fashion. Comparison of the gp21 structure with the structures of other retroviral TMs contrasts the conserved nature of the coiled coil-forming region and adjacent disulfide-bonded loop with the variable nature of the C-terminal ectodomain segment. The structure points to these features having evolved to enable the dual roles of retroviral TMs: conserved fusion function and an ability to anchor diverse surface-exposed subunit structures to the virion envelope and infected cell surface. The structure of gp21 implies that the N-terminal fusion peptide is in close proximity to the C-terminal transmembrane domain and likely represents a postfusion conformation.