Higher-resolution structure of the human insulin receptor ectodomain: Multi-modal inclusion of the insert domain

Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. However, only a low-resolution (3.8 Å) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. Here, we revise this structure using new diffraction data to 3.3 Å resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding.

The structure of glycosaminoglycans and their interactions with proteins

Glycosaminoglycans (GAGs) are important complex carbohydrates that participate in many biological processes through the regulation of their various protein partners. Biochemical, structural biology and molecular modelling approaches have assisted in understanding the molecular basis of such interactions, creating an opportunity to capitalize on the large structural diversity of GAGs in the discovery of new drugs. The complexity of GAG–protein interactions is in part due to the conformational flexibility and underlying sulphation patterns of GAGs, the role of metal ions and the effect of pH on the affinity of binding. Current understanding of the structure of GAGs and their interactions with proteins is here reviewed: the basic structures and functions of GAGs and their proteoglycans, their clinical significance, the three-dimensional features of GAGs, their interactions with proteins and the molecular modelling of heparin binding sites and GAG–protein interactions. This review focuses on some key aspects of GAG structure–function relationships using classical examples that illustrate the specificity of GAG–protein interactions, such as growth factors, anti-thrombin, cytokines and cell adhesion molecules. New approaches to the development of GAG mimetics as possible new glycotherapeutics are also briefly covered.

Dual yolk-shell structure of carbon and silica-coated silicon for high-performance lithium-ion batteries

Silicon batteries have attracted much attention in recent years due to their high theoretical capacity, although a rapid capacity fade is normally observed, attributed mainly to volume expansion during lithiation. Here, we report for the first time successful synthesis of Si/void/SiO2/void/C nanostructures. The synthesis strategy only involves selective etching of SiO2 in Si/SiO2/C structures with hydrofluoric acid solution. Compared with reported results, such novel structures include a hard SiO2-coated layer, a conductive carbon-coated layer, and two internal void spaces. In the structures, the carbon can enhance conductivity, the SiO2 layer has mechanically strong qualities, and the two internal void spaces can confine and accommodate volume expansion of silicon during lithiation. Therefore, these specially designed dual yolk-shell structures exhibit a stable and high capacity of 956 mA h g−1 after 430 cycles with capacity retention of 83%, while the capacity of Si/C core-shell structures rapidly decreases in the first ten cycles under the same experimental conditions. The novel dual yolk-shell structures developed for Si can also be extended to other battery materials that undergo large volume changes.

When and why threats go undetected: Impacts of event rate and shift length on threat detection accuracy during airport baggage screening

Objective: We aimed to assess the impact of task demands and individual characteristics on threat detection in baggage screeners. Background: Airport security staff work under time constraints to ensure optimal threat detection. Understanding the impact of individual characteristics and task demands on performance is vital to ensure accurate threat detection. Method: We examined threat detection in baggage screeners as a function of event rate (i.e., number of bags per minute) and time on task across 4 months. We measured performance in terms of the accuracy of detection of Fictitious Threat Items (FTIs) randomly superimposed on X-ray images of real passenger bags. Results: Analyses of the percentage of correct FTI identifications (hits) show that longer shifts with high baggage throughput result in worse threat detection. Importantly, these significant performance decrements emerge within the first 10 min of these busy screening shifts only. Conclusion: Longer shift lengths, especially when combined with high baggage throughput, increase the likelihood that threats go undetected. Application: Shorter shift rotations, although perhaps difficult to implement during busy screening periods, would ensure more consistently high vigilance in baggage screeners and, therefore, optimal threat detection and passenger safety.

The Pandolf load carriage equation is a poor predictor of metabolic rate while wearing explosive ordnance disposal protective clothing

This investigation aimed to quantify metabolic rate when wearing an explosive ordnance disposal (EOD) ensemble (~33kg) during standing and locomotion; and determine whether the Pandolf load carriage equation accurately predicts metabolic rate when wearing an EOD ensemble during standing and locomotion. Ten males completed 8 trials with metabolic rate measured through indirect calorimetry. Walking in EOD at 2.5, 4.0 and 5.5km·h−1 was significantly (p < 0.05) greater than matched trials without the EOD ensemble by 49% (127W), 65% (213W) and 78% (345W), respectively. Mean bias (95% limits of agreement) between predicted and measured metabolism during standing, 2.5, 4 and 5.5km·h−1 were 47W (19 to 75W); −111W (−172 to −49W); −122W (−189 to −54W) and −158W (−245 to −72W), respectively. The Pandolf equation significantly underestimated measured metabolic rate during locomotion. These findings have practical implications for EOD technicians during training and operation and should be considered when developing maximum workload duration models and work-rest schedules.

Long-term effects of physical activity level on changes in healthy body mass index over 12 years in young adult women

Objectives To examine the effects of overall level and timing of physical activity (PA) on changes from a healthy body mass index (BMI) category over 12 years in young adult women. Patients and Methods Participants in the Australian Longitudinal Study on Women's Health (younger cohort, born 1973-1978) completed surveys between 2000 (age 22-27 years) and 2012 (age 34-39 years). Physical activity was measured in 2000, 2003, 2006, and 2009 and was categorized as very low, low, active, or very active at each survey, and a cumulative PA score for this 9-year period was created. Logistic regression was used to examine relationships between PA accumulated across all surveys (cumulative PA model) and PA at each survey (critical periods PA model), with change in BMI category (from healthy to overweight or healthy to obese) from 2000 to 2012. Results In women with a healthy BMI in 2000, there were clear dose-response relationships between accumulated PA and transition to overweight (P=.03) and obesity (P<.01) between 2000 and 2012. The critical periods analysis indicated that very active levels of PA at the 2006 survey (when the women were 28-33 years old) and active or very active PA at the 2009 survey (age 31-36 years) were most protective against transitioning to overweight and obesity. Conclusion These findings confirm that maintenance of very high PA levels throughout young adulthood will significantly reduce the risk of becoming overweight or obese. There seems to be a critical period for maintaining high levels of activity at the life stage when many women face competing demands of caring for infants and young children.