Equilibrium conformational ensemble of the intrinsically disordered peptide n16N: linking subdomain structures and function in nacre

n16 is a framework protein family associated with biogenic mineral stabilization, thought to operate at three key interfaces in nacre: protein/β-chitin, protein/protein, and protein/CaCO3. The N-terminal half of this protein, n16N, is known to be active in conferring this mineral stabilization and organization. While some details relating to the stabilization and organization of the mineral are known, the molecular mechanisms that underpin these processes are not yet established. To provide these molecular-scale details, here we explore current hypotheses regarding the possible subdomain organization of n16N, as related to these three interfaces in nacre, by combining outcomes of Replica Exchange with Solute Tempering molecular dynamics simulations with NMR experiments, to investigate the conformational ensemble of n16N in solution. We verify that n16N lacks a well-defined secondary structure, both with and without the presence of Ca(2+) ions, as identified from previous experiments. Our data support the presence of three different, functional subdomains within n16N. Our results reveal that tyrosine, chiefly located in the center of the peptide, plays a multifunctional role in stabilizing conformations of n16N, for intrapeptide and possibly interpeptide interactions. Complementary NMR spectroscopy data confirm the participation of tyrosine in this stabilization. The C-terminal half of n16N, lacking in tyrosine and highly charged, shows substantive conformational diversity and is proposed as a likely site for nucleation of calcium carbonate. Finally, dominant structures from our predicted conformational ensemble suggest the presentation of key residues thought to be critical to the selective binding to β-chitin surfaces.

Motivation and cognitive load in the flipped classroom : definition, rationale and a call for research

Flipped classroom approaches remove the traditional transmissive lecture and replace it with active in-class tasks and pre-/post-class work. Despite the popularity of these approaches in the media, Google search, and casual hallway chats, there is very little evidence of effectiveness or consistency in understanding what a flipped classroom actually is. Although the flipped terminology is new, some of the approaches being labelled ‘flipped’ are actually much older. In this paper, we provide a catch-all definition for the flipped classroom, and attempt to retrofit it with a pedagogical rationale, which we articulate through six testable propositions. These propositions provide a potential agenda for research about flipped approaches and form the structure of our investigation. We construct a theoretical argument that flipped approaches might improve student motivation and help manage cognitive load. We conclude with a call for more specific types of research into the effectiveness of the flipped classroom approach.

Dancing with inter-disciplinarity: strategies and practices in higher education dance drama and music

The rise of inter-disciplinarity has not occurred without debate and controversy. Often responding to government agendas, it is not uncommon for university research strategies to include inter-disciplinarity by default, by supporting multidisciplinary collaborations across the institution, nationally and internationally – industry and business being a particular focus. Beginning from the premise that Inter-disciplinary is where students/staff from more than one discipline learn with, from and about one another through a common activity, usually in the context of practice, this report documents the findings of a recent research project aimed to document ways in which inter-disciplinary approaches were active in universities, how they were resourced, what made them effective, and in what ways they are limited.

The role and regulation of erythropoietin (EPO) and its receptor in skeletal muscle: how much do we really know?

Erythropoietin (EPO) primarily activates erythroid cell proliferation and growth and is active in several types of non-hematopoietic cells via its interaction with the EPO-receptor (EPO-R). This review focuses on the role of EPO in skeletal muscle. The EPO-R is expressed in skeletal muscle cells and EPO may promote myoblast differentiation and survival via the activation of the same signaling cascades as in hematopoietic cells, such as STAT5, MAPK and Akt. Inconsistent results exist with respect to the detection of the EPO-R mRNA and protein in muscle cells, tissue and across species and the use of non-specific EPO-R antibodies contributes to this problem. Additionally, the inability to reproducibly detect an activation of the known EPO-induced signaling pathways in skeletal muscle questions the functionality of the EPO-R in muscle in vivo. These equivocal findings make it difficult to distinguish between a direct effect of EPO on skeletal muscle, via the activation of its receptor, and an indirect effect resulting from a better oxygen supply to the muscle. Consequently, the precise role of EPO in skeletal muscle and its regulatory mechanism/s remain to be elucidated. Further studies are required to comprehensively establish the importance of EPO and its function in skeletal muscle health.

Enterprise localization practices and their implication for knowledge management in foreign participation in the Chinese construction sector

Foreign firms active in the Chinese construction industry find themselves in a competitive environment unlike the environments in which they operate back home. Adaptations are therefore required in order that firms retain competitive leverage while integrating into the circumstances of the Chinese market. Since these firms primarily compete on superior knowledge capabilities it is instructive to understand how adaptations both serve to transfer propriety capabilities to China while adapting to the knowledge characteristics of the Chinese market into which those capabilities are transplanted. Five localizing parameters across which adaptations take place are identified in this paper and rates of localization are tabulated for 60 foreign firms active in the Chinese construction industry. Revealed localizing behaviors are then analyzed in the light of existing literature for explanatory power. It is concluded that in order to be strategically competitive firms must not only retain knowledge differentials, but that the knowledge must be coded and disseminated in a manner suited to the environment in which it is to be utilized.

Too hot to move? Objectively assessed seasonal changes in Australian children's physical activity

BACKGROUND: Seasonal variations may influence children's physical activity patterns. The aim of this study was to examine how children's objectively-measured physical activity differed across seasons, and whether different seasonal patterns were observed for boys and girls. METHODS: Three hundred and twenty-six children aged 8-11 years from nine primary schools in Melbourne, Australia, participated in the study. Physical activity was measured every 15-s using hip-mounted GT3X+ ActiGraph accelerometers for seven consecutive days in the Winter (n = 249), Spring (n = 221), Summer (n = 174) and Autumn (n = 152) school terms. Time spent in moderate (MPA), vigorous (VPA) and moderate- to vigorous-intensity physical activity (MVPA) at each time point was derived using age-specific cut-points. Meteorological data (maximum temperature, precipitation, daylight hours) were obtained daily during each season. Longitudinal data were analysed using multilevel analyses, adjusted for age, sex, accelerometer wear time, number of valid days, and meteorological variables. RESULTS: Compared to Winter, children engaged in significantly less MPA (-5.0 min) and MVPA (-7.8 min) in Summer. Girls engaged in less MVPA in Spring (-18 min) and Summer (-9.2 min) and more MVPA in Autumn (9.9 min) compared to Winter. Significant changes in MPA and VPA bout frequency and duration were also observed. Significant decreases in VPA bout frequency (3.4 bouts) and duration (2.6 min) were observed for girls in Spring compared to Winter. No significant seasonal changes were observed for boys for all intensities and physical activity accumulation. CONCLUSIONS: Physical activity decreased in Summer compared to Winter, contrasting previous research that typically reports that children are most active in summer. Greater fluctuations were observed for girls' activity levels. In addition, girls' activity duration and bouts appeared to be more susceptible to seasonal changes compared to boys. The results suggest that strategies to promote physical activity may be needed in Australia during the hot summer months, particularly for girls.

A new evidence-based approach to weight management in primary care: the Counterweight Programme

Background/Aims Obesity has become a global epidemic, and a major preventable cause of morbidity and mortality. Management strategies and treatment protocols are however poorly developed and evaluated. The aim of the Counterweight Programme is to develop an evidence-based model for the management of obesity in primary care.

Methods The Counterweight Programme is based on the theoretical model of Evidence-Based Quality Assessment aimed at improving the management of obese adults (18–75 years) in primary care. The model consists of four phases: (1) practice audit and needs assessment, (2) practice support and training, (3) practice nurse-led patient intervention, and (4) evaluation. Patient intervention consisted of screening and treatment pathways incorporating evidence-based approaches, including patient-centred goal setting, prescribed eating plans, a group programme, physical activity and behavioural approaches, anti-obesity medication and weight maintenance strategies. Weight Management Advisers who are specialist obesity dietitians facilitated programme implementation. Eighty practices were recruited of which 18 practices were randomized to act as controls and receive deferred intervention 2 years after the initial audit.

Results By February 2004, 58 of the 62 (93.5%) intervention practices had been trained to run the intervention programme, 47 (75.8%) practices were active in implementing the model and 1256 patients had been recruited (74% female, 26% male, mean age 50.6 years, SD 14). At baseline, 75% of patients had at one or more co-morbidity, and the mean body mass index (BMI) was 36.9 kg/m2 (SD 5.4). Of the 1256 patients recruited, 91% received one of the core lifestyle interventions in the first 12 months. For all patients followed up at 12 months, 34% achieved a clinical meaningful weight loss of 5% or more. A total of 51% of patients were classed as compliant in that they attended the required level of appointments in 3, 6, and 12 months. For fully compliant patients, weight loss improved with 43% achieving a weight loss of 5% or more at 12 months.

Conclusion The Counterweight Programme is an evidence-based weight management model which is feasible to implement in primary care.

Longitudinal study of daily variation of rats' behavior in the elevated plus-maze

We conducted a longitudinal study about daily variation of Wistar male rats' behavior in the elevated plus-maze (EPM) evaluated in the 1st, 2nd, 3rd, 6th, 12th, and 18th months of life. Animals were submitted to the plus-maze in 12 sessions at 2-h intervals (n=72, 6 per time point). Spontaneous rest-activity rhythm of four animals was assessed by observation of 24-h videotape records. Time series were analyzed by Cosinor method. Behavioral rates on the six occasions and in light and dark phases were compared by means of two-way ANOVA with repeated measures. Exploratory behavior in EPM was smaller in the light phase and in older animals. Higher values of open and closed arms exploration were observed in the first and third months of the dark phase, and in the first month of the light phase. Adjustment to the 24-h period was significant at all stages for rest-activity data, number of entries in closed arms, and time on center, and for three to five stages for open-arm exploration. In general, 24 h variability was more pronounced in younger animals compared with older ones. The present study showed that: (1) a significant amount of total variability of the behavioral indexes analyzed could be attributed to 24 h variation, (2) light/dark phases differences in EPM exploration were present at all developmental stages, (3) older Wistar rats explored less the EPM and were less active in their home cage compared with younger ones, and (4) behavioral indexes (EPM) decrease was phase related and partially related to a reorganization of rest-activity rhythm. (C) 2003 Elsevier B.V. All rights reserved.

In vitro Activity of Daptomycin, Linezolid and Rifampicin on Staphylococcus epidermidis Biofilms

Owing to their massive use, Staphylococcus epidermidis has recently developed significant resistance to several antibiotics, and became one of the leading causes of hospital-acquired infections. Current antibiotics are typically ineffective in the eradication of bacteria in biofilm-associated persistent infections. Accordingly, the paucity of effective treatment against cells in this mode of growth is a key factor that potentiates the need for new agents active in the prevention or eradication of biofilms. Daptomycin and linezolid belong to the novel antibiotic therapies that are active against gram-positive cocci. on the other hand, rifampicin has been shown to be one of the most potent, prevalent antibiotics against S. epidermidis biofilms. Therefore, the main aim of this study was to study the susceptibility of S. epidermidis biofilm cells to the two newer antimicrobial agents previously mentioned, and compare the results obtained with the antimicrobial effect of rifampicin, widely used in the prevention/treatment of indwelling medical device infections. To this end the in vitro activities of daptomycin, linezolid, and rifampicin on S. epidermidis biofilms were accessed, using these antibiotics at MIC and peak serum concentrations. The results demonstrated that at MIC concentration, rifampicin was the most effective antibiotic tested. At peak serum concentration, both strains demonstrated similar susceptibility to rifampicin and daptomycin, with colony-forming units (CFUs) reductions of approximately 3-4 log(10), with a slightly lower response to linezolid, which was also more strain dependent. However, considering all the parameters studied, daptomycin was considered the most effective antibiotic tested, demonstrating an excellent in vitro activity against S. epidermidis biofilm cells. In conclusion, this antibiotic can be strongly considered as an acceptable therapeutic option for S. epidermidis biofilm-associated infections and can represent a potential alternative to rifampicin in serious infections where rifampicin resistance becomes prevalent.

Lek phenology of the White-bearded Manakin (Manacus manacus, Aves: Passeriformes: Pipridae) in a subtropical region

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Regulation of Social Hierarchy Over Time in Colonies of the Primitive Eusocial Wasp Mischocyttarus (Monocyttarus) cassununga. Von Ihering, 1903 (Hymenoptera, Vespidae)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Copia Retrotransposon in the Zaprionus Genus: Another Case of Transposable Element Sharing with the Drosophila melanogaster Subgroup

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Testosterone Promotes an Anabolic Increase in the Rat Female Prostate (Skene's Paraurethral Gland) Which Acquires a Male Ventral Prostate Phenotype

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Multiple invasions of Gypsy and Micropia retroelements in genus Zaprionus and melanogaster subgroup of the genus Drosophila

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Synthesis and in vitro evaluation of potential antichagasic dipeptide prodrugs of primaquine

American trypanosomiasis (Chagas' disease) is an endemic parasitic disease afflicting more than 20 million people in Latin America. Currently, therapy is unsatisfactory and only two drugs are available. Primaquine, an antimalarial drug, has trypanocidal activity. Dipeptide derivatives of primaquine, Phe-Arg-PQ, Lys-Arg-PQ, and Phe-Ala-PQ, were synthesized. The choice of the peptides was based on the primary specificity of cruzipain, the major cysteine proteinase from T. cruzi. The prodrugs obtained were tested on the LLC-MK2 cell culture infected with trypomastigotes forms of T. cruzi Phe-Arg-PQ, Lys-Arg-PQ, and Phe-Ala-PQ were active in all stages.