The Topology,in Model Membranes,of the Core Peptide Derived from the T‐Cell Receptor Transmembrane Domain

The T‐cell receptor–CD3 complex (TCR–CD3) serves a critical role in protecting organisms from infectious agents. The TCR is a heterodimer composed of α‐ and β‐chains, which are responsible for antigen recognition. Within the transmembrane domain of the α‐subunit, a region has been identified to be crucial for the assembly and function of the TCR. This region, termed core peptide (CP), consists of nine amino acids (GLRILLLKV), two of which are charged (lysine and arginine) and are crucial for the interaction with CD3. Earlier studies have shown that a synthetic peptide corresponding to the CP sequence can suppress the immune response in animal models of T‐cell‐mediated inflammation, by disrupting proper assembly of the TCR. As a step towards the understanding of the source of the CP activity, we focused on CP in egg phosphatidylcholine/cholesterol (9:1, mol/mol) model membranes and determined its secondary structure, oligomerization state, and orientation with respect to the membrane. To achieve this goal, 15‐residue segments of TCRα, containing the CP, were synthesized and spin‐labeled at different locations with a nitroxide derivative. Electron spin‐echo envelope modulation spectroscopy was used to probe the position and orientation of the peptides within the membrane, and double electron–electron resonance measurements were used to probe its conformation and oligomerization state. We found that the peptide is predominantly helical in a membrane environment and tends to form oligomers (mostly dimers) that are parallel to the membrane plane.     

Design,Synthesis, and Characterization of Macrocyclic Inhibitors of the Proprotein Convertase Furin

The activation of viral glycoproteins by the host protease furin is an essential step in the replication of numerous pathogenic viruses. Thus, effective inhibitors of furin could serve as broad-spectrum antiviral drugs. A crystal structure of an inhibitory hexapeptide derivative in complex with furin served as template for the rational design of various types of new cyclic inhibitors. Most of the prepared derivatives are relatively potent furin inhibitors with inhibition constants in the low nanomolar or even sub-nanomolar range. For seven derivatives the crystal structures in complex with furin could be determined. In three complexes, electron density was found for the entire inhibitor. In the other cases the structures could be determined only for the P6/P5-P1 segments, which directly interact with furin. The cyclic derivatives together with two non-cyclic reference compounds were tested as inhibitors of the proteolytic activation and replication of respiratory syncytial virus in cells. Significant antiviral activity was found for both linear reference inhibitors, whereas a negligible efficacy was determined for the cyclic derivatives.     

Organometallic DNA–B12 Conjugates as Potential Oligonucleotide Vectors: Synthesis and Structural and Binding Studies with Human Cobalamin-Transport Proteins

The synthesis and structural characterization of Co-(dN)₂₅-Cbl (Cbl: cobalamin; dN: deoxynucleotide) and Co-(dN)₃₉-Cbl, which are organometallic DNA–B₁₂ conjugates with single DNA strands consisting of 25 and 39 deoxynucleotides, respectively, and binding studies of these two DNA–Cbl conjugates to three homologous human Cbl transporting proteins, transcobalamin (TC), intrinsic factor (IF), and haptocorrin (HC), are reported. This investigation tests the suitability of such DNA–Cbls for the task of eventual in vivo oligonucleotide delivery. The binding of DNA–Cbl to TC, IF, and HC was investigated in competition with either a fluorescent Cbl derivative and Co-(dN)₂₅-Cbl, or radiolabeled vitamin B₁₂ (⁵⁷Co-CNCbl) and Co-(dN)₂₅-Cbl or Co-(dN)₃₉-Cbl. Binding of the new DNA–Cbl conjugates was fast and tight with TC, but poorer with HC and IF, which extends a similar original finding with the simpler DNA–Cbl, Co-(dN)₁₈-Cbl. The contrasting affinities of TC versus IF and HC for the DNA–Cbl conjugates are rationalized herein by a stepwise mechanism of Cbl binding. Critical contributions to overall affinity result from gradual conformational adaptations of the Cbl-binding proteins to the DNA–Cbl, which is first bound to the respective β domains. This transition is fast with TC, but slow with IF and HC, with which weaker binding results. The invariably tight interaction of the DNA–Cbl conjugates with TC makes the Cbl moiety a potential natural vector for the specific delivery of oligonucleotide loads from the blood into cells.     

Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure

One-quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI)—an abrupt reduction or loss of kidney function associated with increased long-term mortality. There is a critical need to identify early and real-time markers of AKI in ADHF; however, to date, no protein biomarkers have exhibited sufficient diagnostic or prognostic performance for widespread clinical uptake. We aimed to identify novel protein biomarkers of AKI associated with ADHF by quantifying changes in protein abundance in the kidneys that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using sequential window acquisition of all theoretical fragment ion spectra–mass spectrometry (SWATH–MS) in kidney cortices from control sheep (n = 5), sheep with established rapid-pacing-induced ADHF (n = 8), and sheep after ~4 weeks recovery from ADHF (n = 7). Of the 790 proteins quantified, we identified 17 candidate kidney injury markers in ADHF, 1 potential kidney marker of ADHF recovery, and 2 potential markers of long-term renal impairment (differential abundance between groups of 1.2–2.6-fold, adjusted p < 0.05). Among these 20 candidate protein markers of kidney injury were 6 candidates supported by existing evidence and 14 novel candidates not previously implicated in AKI. Proteins of differential abundance were enriched in pro-inflammatory signalling pathways: glycoprotein VI (activated during ADHF development; adjusted p < 0.01) and acute phase response (repressed during recovery from ADHF; adjusted p < 0.01). New biomarkers for the early detection of AKI in ADHF may help us to evaluate effective treatment strategies to prevent mortality and improve outcomes for patients.     

Batch treatment of liquid fraction of pig slurry by intermittent aeration: process simulation and microbial community analysis

BACKGROUND: Manure treatment in intensive livestock farming is required to reduce the risk of negative environmental impacts by nitrogen disposal. Biological removal through intermittent aeration in a single bioreactor is a suitable method for this purpose. The characteristic operation based on the alternation of oxic/anoxic phases confers these systems with certain particularities in terms of process modelling and of understanding the microbial interactions. RESULTS: The performance of a sequencing batch reactor (SBR) treating raw liquid fraction of pig slurry (LFPS) under loading rates of 0.13 g N L^?1 d^?1 was studied. Three different aeration strategies were applied: (1) constant airflow; (2) dissolved oxygen (DO) set‐point; and (3) DO‐based real‐time control. The comparatively low aeration intensity applied throughout the third strategy resulted in the process being performed mainly via nitrite, implying a reduction on the requirements of organic carbon and oxygen. However, a decrease in the nitrification rate was observed under those conditions. Experimental results were satisfactorily simulated by a mathematical model focused on organic carbon and nitrogen removal. Microbial community structure analysis through denaturing gradient gel electrophoretic profiling of 16S rDNA genes showed that the aeration exerted a strong influence on the dominant microbial populations. The presence of the ammonia‐oxidizing species Nitrosomonas europaea, and of denitrifying bacteria related to Thauera sp. and Ralstonia sp., was detected in the strategy at low DO. CONCLUSION: Dependence of model statement and parameter values on the bioreactor operational patterns and piggery wastewater composition was evidenced. Oxygen limitation was responsible for a significant microbial shift in SBR treating LFPS. Copyright © 2009 Society of Chemical Industry     

Winery grape-residue extract: Effects on quality and sensory attributes of cooked chicken meat

Sensory analysis, instrumental color, pH, and thiobarbituric acid reactive substances (TBARS) were determined on cooked chicken meat with and without grape seed extract during refrigerated storage. The effectiveness of extracts of winery grape residue from the grape varieties ‘Isabel’ and ‘Niagara’ were tested to evaluate their effectiveness at delaying lipid oxidation in cooked chicken meat and stored under refrigeration (4±1°C). The samples were aerobically and vacuum packaged and stored for 14 days. ‘Isabel’ grape extract (IGE) and ‘Niagara’ grape extract (NGE) proved effective at promoting oxidative stability when applied at concentrations of 40 or 60 mg of gallic acid equivalents (GAE)/kg, with results similar to the synthetic antioxidant butylated hydroxytoluene (BHT). The antioxidant efficiency of the extracts was highly dependent on the concentration used. The addition of grape-residue extracts combined with vacuum packaging proved to be a good method for increasing lipid stability in cooked chicken meat stored under refrigeration.     

The mental health of men with a psychiatric disorder or traumatic brain injury: Wives' labeling and husbands' perceived control.

Objective: To investigate the relations among wives' labeling of their husbands' psychiatric disorder or brain injury as an organic illness, the husbands' perceived control over their disabilities, and the husbands' mental health. Participants: 57 male clients of the Department of Rehabilitation, Israel's Ministry of Defence (26 with a psychiatric disorder and 31 with a traumatic brain injury) and their wives. Measures: Illness Labeling Questionnaire, the Perceived Control Over Illness Questionnaire, and the Mental Health Inventory. Results: Husbands' mental health was low but did not differ according to disability; wives' labeling of husbands' condition was negatively related to the husbands' mental health; husbands' perceived control was positively related to their mental health for both disabilities. Conclusion: Organic illness labels, even when adopted by the wives of the persons with the disability, seem to be negatively related to that person's mental health, whereas perceived control over a mental disorder or a brain injury seems to contribute positively to mental health, independently of how the disorder or injury is labeled. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of polyvinylchloride films and edible starch coatings on quality aspects of refrigerated Brussels sprouts

To extend shelf life, the effects of polyvinylchloride film (PVC) and edible coatings on quality aspects of refrigerated Brussels sprouts were studied. Starch-based coatings were formulated using glycerol (G), sorbitol (S) or glycerol plus sunflower oil (O). Sprouts so treated as well as uncoated ones were placed on expanded polystyrene trays. Combinations of PVC and coatings (treatments named G-PVC, S-PVC and O-PVC) were also tested. Uncovered trays were maintained as controls. All packages were stored at 0 °C for 42 days and samples were removed every 14 days to determine commercial acceptability, weight loss, surface colour (of sprouts’ heads and bases) and texture. Sprouts in all treatments maintained optimum quality conditions over the first 14 days. At the end of storage, browning of cut zones and losses in weight and firmness were minimised in PVC-packaged sprouts, particularly in G-PVC. Therefore, PVC and G-PVC treatments were selected to evaluate some nutritional quality components. Ascorbic acid and total flavonoid contents remained almost constant while radical scavenging activity increased after 42 days of storage. Thus, PVC and G-PVC treatments showed the best performance for long-term refrigerated storage of Brussels sprouts.     

Participative goal-setting: Social, motivational, and cognitive factors.

Examined 3 explanations of why participation in goal setting may lead to increased performance—the social factor of group discussion, the motivational factor of involvement in goal setting, and the cognitive factor of information. A 2?×?2?×?2 experimental design (low and high levels of group discussion, involvement, and information) was used to study 96 predominantly male white collar employees (aged 23–58 yrs) who worked on a simulated personnel selection task. Results indicate that the social and motivational factors of participation increased performance quantity, incidental learning, goal acceptance, group commitment, and satisfaction. The motivational and cognitive factors significantly contributed to performance quality but the cognitive factor did not significantly affect performance quantity and work attitudes. It is suggested that a combination of the 3 factors leads to the highest level of performance. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)