Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin

Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagnostics. We produced and characterized nine monoclonal antibodies that showed significant neutralizing activities against H1 subtype influenza viruses, and determined the complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01) and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall structure of the complex was essentially identical to the previously determined KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily accessible head regions of HA, revealing broadly shared and conserved antigenic determinants among H1 subtypes. The beta-strands constituted by Ser110-Glu115 and Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza strain. Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus

Mycobacterial Evolution Intersects With Host Tolerance

Over the past 200 years, tuberculosis (TB) has caused more deaths than any other infectious disease, likely infecting more people than it has at any other time in human history. Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, is an obligate human pathogen that has evolved through the millennia to become an archetypal human-adapted pathogen. This review focuses on the evolutionary framework by which Mtb emerged as a specialized human pathogen and applies this perspective to the emergence of specific lineages that drive global TB burden. We consider how evolutionary pressures, including transmission dynamics, host tolerance, and human population patterns, may have shaped the evolution of diverse mycobacterial genomes

Planning and Designing Walkable Cities: A Smart Approach

Walking may be considered one of the most sustainable and democratic ways of travelling within a city, thus providing benefits not only to pedestrians but also to the urban environment. Besides, walking is also one of the means of transport most likely subjected to factors outside an individual\u2019s control, like social or physical abilities to walk and the presence of comfortable and safe street infrastructures and services. Therefore, improving urban conditions provided to pedestrians has positive impacts on walkability. At the same time technological solutions and innovations have the power to encourage and support people to walk by overcoming immaterial barriers due to a lack of information or boring travel and they give to decision makers the possibility to gain data to understand how and where people travel. Merging these two dimensions into a unique approach can drastically improve accessibility, attractiveness, safety, comfort and security of urban spaces. In this context, this paper aims to draw a more multifaceted context for walkability, where new technologies assume a key role for introducing new approaches to pedestrian paths planning and design and thus for enhancing this mode of transport. Indeed, by combining more traditional spatial-based and perceptual analysis of the urban environment with technological applications and social media exploitation there will be room to better support the decision on and to enhance satisfaction of walking as well as to easier plan and design more walkable cities

Circulating proteolytic signatures of chemotherapy-induced cell death in humans discovered by N-terminal labeling

It is known that many chemotherapeutics induce cellular apoptosis over hours to days. During apoptosis, numerous cellular proteases are activated, most canonically the caspases. We speculated that detection of proteolytic fragments released from apoptotic cells into the peripheral blood may serve as a unique indicator of chemotherapy-induced cell death. Here we used an enzymatic labeling process to positively enrich free peptide α-amines in the plasma of hematologic malignancy patients soon after beginning treatment. This N-terminomic approach largely avoids interference by high-abundance proteins that complicate traditional plasma proteomic analyses. Significantly, by mass spectrometry methods, we found strong biological signatures of apoptosis directly in the postchemotherapy plasma, including numerous caspase-cleaved peptides as well as relevant peptides from apoptotic and cell-stress proteins second mitochondria-derived activator of caspases, HtrA serine peptidase 2, and activating transcription factor 6. We also treated hematologic cancer cell lines with clinically relevant chemotherapeutics and monitored proteolytic fragments released into the media. Remarkably, many of these peptides coincided with those found in patient samples. Overall, we identified 153 proteolytic peptides in postchemotherapy patient plasma as potential indicators of cellular apoptosis. Through targeted quantitative proteomics, we verified that many of these peptides were indeed increased post- vs. prechemotherapy in additional patients. Our findings reveal that numerous proteolytic fragments are released from dying tumor cells. Monitoring posttreatment proteolysis may lead to a novel class of inexpensive, rapid biomarkers of cell death

The Escherichia coli transcriptome mostly consists of independently regulated modules

Underlying cellular responses is a transcriptional regulatory network (TRN) that modulates gene expression. A useful description of the TRN would decompose the transcriptome into targeted effects of individual transcriptional regulators. Here, we apply unsupervised machine learning to a diverse compendium of over 250 high-quality Escherichia coli RNA-seq datasets to identify 92 statistically independent signals that modulate the expression of specific gene sets. We show that 61 of these transcriptomic signals represent the effects of currently characterized transcriptional regulators. Condition-specific activation of signals is validated by exposure of E. coli to new environmental conditions. The resulting decomposition of the transcriptome provides: a mechanistic, systems-level, network-based explanation of responses to environmental and genetic perturbations; a guide to gene and regulator function discovery; and a basis for characterizing transcriptomic differences in multiple strains. Taken together, our results show that signal summation describes the composition of a model prokaryotic transcriptome

Saffold virus is able to productively infect primate and rodent cell lines and induces apoptosis in these cells

10.1038/emi.2014.15Emerging Microbes and Infections3

Bicycle Use for Transport in an Australian and a Belgian City: Associations with Built-Environment Attributes

The walkability attributes of neighborhood environments (residential density, land use mixture, and connectedness of streets) have been found to be associated with higher rates of walking. However, relatively less is known about the associations of walkability attributes with bicycle use for transport. We examined the relationships between adults' bicycle use for transport and measures of neighborhood walkability in two settings: an Australian city (Adelaide) with low rates of bicycle use and a Belgian city (Ghent) with high rates of bicycle use. A total of 2,159 and 382 participants were recruited in Adelaide and Ghent, respectively. A walkability index was derived from objectively measured data in Adelaide, while a similar index was derived from perceived measures in Ghent. Logistic regression models were employed to examine associations of bicycle use with different levels of walkability. There were higher rates of bicycle ownership for Ghent compared to Adelaide participants (96% versus 61%), and there was a higher prevalence of bicycle use for transport for Ghent compared to Adelaide participants (50% vs. 14%). Despite the large differences in bicycle ownership and use, living in a high-walkable neighborhood was associated with significantly higher odds of bicycle use for transport in both cities, after adjusting for relevant confounding factors. Built-environment innovations that are increasingly being advocated by health authorities and transport planners, primarily to promote higher rates of walking for transport, should also impact positively on bicycle use

Preventing weight gain: the baseline weight related behaviors and delivery of a randomized controlled intervention in community based women

<p>Abstract</p> <p>Background</p> <p>Women aged 25–45 years represent a high risk group for weight gain and those with children are at increased risk because of weight gain associated with pregnancy and subsequent lifestyle change. Average self-reported weight gain is approximately 0.60 kg per year, and weight gain is associated with increased risk of chronic disease. There are barriers to reaching, engaging and delivering lifestyle interventions to prevent weight gain in this population.</p> <p>Methods</p> <p>This study investigated the baseline weight related behaviors and feasibility of recruiting and delivering a low intensity self-management lifestyle intervention to community based women with children in order to prevent weight gain, compared to standard education. The recruitment and delivery of the cluster-randomized controlled intervention was in conjunction with 12 primary (elementary) schools. Baseline data collection included demographic, anthropometric, behavioral and biological measures.</p> <p>Results</p> <p>Two hundred and fifty community based women were randomized as clusters to intervention (n = 127) or control (n = 123). Mean age was 40.4 years (SD 4.7) and mean BMI 27.8 kg/m²(SD 5.6). All components of this intervention were successfully delivered and retention rates were excellent, 97% at 4 months.</p> <p>Nearly all women (90%) reported being dissatisfied with their weight and 72% attempted to self-manage their weight. Women were more confident of changing their diet (mean score 3.2) than physical activity (mean score 2.7). This population perceived they were engaging in prevention behaviors, with 71% reporting actively trying to prevent weight gain, yet they consumed a mean of 68 g fat/day (SD30 g) and 27 g saturated fat/day (SD12 g) representing 32% and 13% of energy respectively. The women had a high rate of dyslipidemia (33%) and engaged in an average of 9187 steps/day (SD 3671).</p> <p>Conclusion</p> <p>Delivery of this low intensity intervention to a broad cross-section of community based women with children is feasible. Women with children are engaging in lifestyle behaviours which do not confer adequate health benefits. They appear to be motivated to attend prevention programs by their interest in weight management. Interventions are required to strengthen and sustain current attempts at achieving healthy lifestyle behaviours in women to prevent weight gain.</p> <p>Trial Registration Number</p> <p>ACTRN 12608000110381</p

Physical environmental factors related to walking and cycling in older adults: the Belgian aging studies

<p>Abstract</p> <p>Background</p> <p>Socio-ecological models emphasize the relationship between the physical environment and physical activity (PA). However, knowledge about this relationship in older adults is limited. Therefore, the present study aims to investigate the relationship between area of residence (urban, semi-urban or rural) and older adults' walking and cycling for transportation and recreation. Additionally, relationships between several physical environmental factors and walking and cycling and possible moderating effects of area of residence, age and gender were studied.</p> <p>Methods</p> <p>Data from 48,879 Flemish older adults collected in 2004-2010 through peer research were analyzed. Walking, cycling and environmental perceptions were assessed using self-administered questionnaires. The Study Service of the Flemish Government provided objective data on municipal characteristics. Multilevel logistic regression analyses were applied.</p> <p>Results</p> <p>Urban participants were more likely to walk daily for transportation compared to rural (OR = 1.43; 95% CI = 1.22, 1.67) and semi-urban participants (OR = 1.32; 95% CI = 1.13, 1.54). Urban participants were less likely to cycle daily for transportation compared to semi-urban participants (OR = 0.72; 95% CI = 0.56, 0.92). Area of residence was unrelated to weekly recreational walking/cycling. Perceived short distances to services (ORs ranging from 1.04 to 1.19) and satisfaction with public transport (ORs ranging from 1.07 to 1.13) were significantly positively related to all walking/cycling behaviors. Feelings of unsafety was negatively related to walking for transportation (OR = 0.93, 95% CI = 0.91, 0.95) and recreational walking/cycling (OR = 0.95, 95% CI = 0.92, 0.97). In females, it was also negatively related to cycling for transportation (OR = 0.94, 95% CI = 0.90, 0.98).</p> <p>Conclusions</p> <p>Urban residents were more likely to walk for transportation daily compared to semi-urban and rural residents. Daily cycling for transportation was less prevalent among urban compared to semi-urban residents. Access to destinations appeared to be important for promoting both walking and cycling for transportation and recreation across all demographic subgroups. Additionaly, feelings of unsafety were associated with lower rates of walking for transportation and walking/cycling for recreation in all subgroups and cycling for transportation in females. No clear patterns emerged for other environmental factors.</p

Assessing the influence of the built environment on physical activity for utility and recreation in suburban metro Vancouver

<p>Abstract</p> <p>Background</p> <p>Physical inactivity and associated co-morbidities such as obesity and cardiovascular disease are estimated to have large societal costs. There is increasing interest in examining the role of the built environment in shaping patterns of physical activity. However, few studies have: (1) simultaneously examined physical activity for leisure and utility; (2) selected study areas with a range of built environment characteristics; and (3) assessed the built environment using high-resolution land use data.</p> <p>Methods</p> <p>Data on individuals used for this study are from a survey of 1602 adults in selected sites across suburban Metro Vancouver. Four types of physical activity were assessed: walking to work/school, walking for errands, walking for leisure and moderate physical activity for exercise. The built environment was assessed by constructing one-kilometre road network buffers around each respondent's postal code. Measures of the built environment include terciles of recreational and park land, residential land, institutional land, commercial land and land use mix.</p> <p>Results</p> <p>Logistic regression analyses showed that walking to work/school and moderate physical activity were not associated with any built environment measure. Living in areas with lower land use mix, lower commercial and lower recreational land increased the odds of low levels of walking for errands. Individuals living in the lower third of land use mix and institutional land were more likely to report low levels of walking for leisure.</p> <p>Conclusions</p> <p>These results suggest that walking for errands and leisure have a greater association with the built environment than other dimensions of physical activity.</p