ASU Scholarship Showcase

Contemporary human populations conform to ecogeographic predictions that animals will become more compact in cooler climates and less compact in warmer ones. However, it remains unclear to what extent this pattern reflects plastic responses to current environments or genetic differences among populations. Analyzing anthropometric surveys of 232,684 children and adults from across 80 ethnolinguistic groups in sub-Saharan Africa, Asia and the Americas, we confirm that body surface-to-volume correlates with contemporary temperature at magnitudes found in more latitudinally diverse samples (Adj. R² = 0.14-0.28). However, far more variation in body surface-to-volume is attributable to genetic population structure (Adj. R² = 0.50-0.74). Moreover, genetic population structure accounts for nearly all of the observed relationship between contemporary temperature and body surface-to-volume among children and adults. Indeed, after controlling for population structure, contemporary temperature accounts for no more than 4% of the variance in body form in these groups. This effect of genetic affinity on body form is also independent of other ecological variables, such as dominant mode of subsistence and household wealth per capita. These findings suggest that the observed fit of human body surface-to-volume with current climate in this sample reflects relatively large effects of existing genetic population structure of contemporary humans compared to plastic response to current environments.

Background: The transition from the home to college is a phase in which emerging adults shift toward more unhealthy eating and physical activity patterns, higher body mass indices, thus increasing risk of overweight/obesity. Currently, little is understood about how changing friendship networks shape weight gain behaviors. This paper describes the recruitment, data collection, and data analytic protocols for the SPARC (Social impact of Physical Activity and nutRition in College) study, a longitudinal examination of the mechanisms by which friends and friendship networks influence nutrition and physical activity behaviors and weight gain in the transition to college life.

Methods: The SPARC study aims to follow 1450 university freshmen from a large university over an academic year, collecting data on multiple aspects of friends and friendship networks. Integrating multiple types of data related to student lives, ecological momentary assessments (EMAs) are administered via a cell phone application, devilSPARC. EMAs collected in four 1-week periods (a total of 4 EMA waves) are integrated with linked data from web-based surveys and anthropometric measurements conducted at four times points (for a total of eight data collection periods including EMAs, separated by ~1 month). University databases will provide student card data, allowing integration of both time-dated data on food purchasing, use of physical activity venues, and geographical information system (GIS) locations of these activities relative to other students in their social networks.

Discussion: Findings are intended to guide the development of more effective interventions to enhance behaviors among college students that protect against weight gain during college.

There are an increasing variety of applications in which peptides are both synthesized and used attached to solid surfaces. This has created a need for high throughput sequence analysis directly on surfaces. However, common sequencing approaches that can be adapted to surface bound peptides lack the throughput often needed in library-based applications. Here we describe a simple approach for sequence analysis directly on solid surfaces that is both high speed and high throughput, utilizing equipment available in most protein analysis facilities. In this approach, surface bound peptides, selectively labeled at their N-termini with a positive charge-bearing group, are subjected to controlled degradation in ammonia gas, resulting in a set of fragments differing by a single amino acid that remain spatially confined on the surface they were bound to. These fragments can then be analyzed by MALDI mass spectrometry, and the peptide sequences read directly from the resulting spectra.

Background: Chemistry and particularly enzymology at surfaces is a topic of rapidly growing interest, both in terms of its role in biological systems and its application in biocatalysis. Existing protein immobilization approaches, including noncovalent or covalent attachments to solid supports, have difficulties in controlling protein orientation, reducing nonspecific absorption and preventing protein denaturation. New strategies for enzyme immobilization are needed that allow the precise control over orientation and position and thereby provide optimized activity.

Methodology/Principal Findings: A method is presented for utilizing peptide ligands to immobilize enzymes on surfaces with improved enzyme activity and stability. The appropriate peptide ligands have been rapidly selected from high-density arrays and when desirable, the peptide sequences were further optimized by single-point variant screening to enhance both the affinity and activity of the bound enzyme. For proof of concept, the peptides that bound to β-galactosidase and optimized its activity were covalently attached to surfaces for the purpose of capturing target enzymes. Compared to conventional methods, enzymes immobilized on peptide-modified surfaces exhibited higher specific activity and stability, as well as controlled protein orientation.

Conclusions/Significance: A simple method for immobilizing enzymes through specific interactions with peptides anchored on surfaces has been developed. This approach will be applicable to the immobilization of a wide variety of enzymes on surfaces with optimized orientation, location and performance, and provides a potential mechanism for the patterned self-assembly of multiple enzymes on surfaces.

Background: Prior studies have shown that using uterotonics to augment or induce labor before arrival at comprehensive Emergency Obstetric and Neonatal Care (CEmONC) settings (henceforth, “outside uterotonics”) may contribute to perinatal mortality in low- and middle-income countries. We estimate its effect on perinatal mortality in rural Bangladesh.

Methods: Using hospital records (23986 singleton term births, Jan 1, 2009-Dec 31, 2015) from rural Bangladesh, we use a logistic regression model to estimate the increased risk of perinatal death from uterotonics administered outside a CEmONC facility.

Results: Among term births (≥37 weeks gestation), the risk of perinatal death adjusted for key confounders is significantly increased among women reporting uterotonic use outside of CEmONC (OR = 3 · 0, 95 % CI = 2 · 4,3 · 7). This increased risk is particularly high for fresh stillbirths (OR = 4 · 0, 95 % CI = 3 · 0,5 · 3) and intrapartum-related causes of early neonatal deaths (birth asphyxia) (OR = 3 · 1, 95 % CI = 2 · 2,4 · 5).

Conclusions: In this sample, outside uterotonic use was associated with substantially increased risk of fresh stillbirths, deaths due to birth asphyxia, and all perinatal deaths. In settings of high uterotonic use outside of controlled settings, substantial improvement in both stillbirth and early neonatal mortality may be made by reducing such use.

Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology.

Background: Improving perinatal health is the key to achieving the Millennium Development Goal for child survival. Recently, several reviews suggest that scaling up available effective perinatal interventions in an integrated approach can substantially reduce the stillbirth and neonatal death rates worldwide. We evaluated the effect of packaged interventions given in pregnancy, delivery and post-partum periods through integration of community- and facility-based services on perinatal mortality.

Methods: This study took advantage of an ongoing health and demographic surveillance system (HDSS) and a new Maternal, Neonatal and Child Health (MNCH) Project initiated in 2007 in Matlab, Bangladesh in half (intervention area) of the HDSS area. In the other half, women received usual care through the government health system (comparison area). The MNCH Project strengthened ongoing maternal and child health services as well as added new services. The intervention followed a continuum of care model for pregnancy, intrapartum, and post-natal periods by improving established links between community- and facility-based services. With a separate pre-post samples design, we compared the perinatal mortality rates between two periods--before (2005-2006) and after (2008-2009) implementation of MNCH interventions. We also evaluated the difference-of-differences in perinatal mortality between intervention and comparison areas.

Results: Antenatal coverage, facility delivery and cesarean section rates were significantly higher in the post- intervention period in comparison with the period before intervention. In the intervention area, the odds of perinatal mortality decreased by 36% between the pre-intervention and post-intervention periods (odds ratio: 0.64; 95% confidence intervals: 0.52-0.78). The reduction in the intervention area was also significant relative to the reduction in the comparison area (OR 0.73, 95% CI: 0.56-0.95; P = 0.018).

Conclusion: The continuum of care approach provided through the integration of service delivery modes decreased the perinatal mortality rate within a short period of time. Further testing of this model is warranted within the government health system in Bangladesh and other low-income countries.

Much research has established reliable cross-population differences in motivations to invest in one's in-group. We compare two current historical-evolutionary hypotheses for this variation based on (1) effective large-scale institutions and (2) pathogen threats by analyzing cross-national differences (N = 122) in in-group preferences measured in three ways. We find that the effectiveness of government institutions correlates with favoring in-group members, even when controlling for pathogen stress and world region, assessing reverse causality, and providing a check on endogeneity with an instrumental variable analysis. Conversely, pathogen stress shows inconsistent associations with in-group favoritism when controlling for government effectiveness. Moreover, pathogen stress shows little to no association with in-group favoritism within major world regions whereas government effectiveness does. These results suggest that variation in in-group preferences across contemporary nation-states is more consistent with a generalized response to institutions that meet basic needs rather than an evolved response dedicated to pathogens.

The relationship between sequence and binding properties of an aptamer for immunoglobulin E (IgE) was investigated using custom DNA microarrays. Single, double and some triple mutations of the aptamer sequence were created to evaluate the importance of specific base composition on aptamer binding. The majority of the positions in the aptamer sequence were found to be immutable, with changes at these positions resulting in more than a 100-fold decrease in binding affinity. Improvements in binding were observed by altering the stem region of the aptamer, suggesting that it plays a significant role in binding. Results obtained for the various mutations were used to estimate the information content and the probability of finding a functional aptamer sequence by selection from a random library. For the IgE-binding aptamer, this probability is on the order of 10^-10 to 10^-9. Results obtained for the double and triple mutations also show that there are no compensatory mutations within the space defined by those mutations. Apparently, at least for this particular aptamer, the functional sequence space can be represented as a rugged landscape with sharp peaks defined by highly constrained base compositions. This makes the rational optimization of aptamer sequences using step-wise mutagenesis approaches very challenging.

Material wealth is a key factor shaping human development and well-being. Every year, hundreds of studies in social science and policy fields assess material wealth in low- and middle-income countries assuming that there is a single dimension by which households can move from poverty to prosperity. However, a one-dimensional model may miss important kinds of prosperity, particularly in countries where traditional subsistence-based livelihoods coexist with modern cash economies. Using multiple correspondence analysis to analyze representative household data from six countries—Nepal, Bangladesh, Ethiopia, Kenya, Tanzania, and Guatemala—across three world regions, we identify a number of independent dimension of wealth, each with a clear link to locally relevant pathways to success in cash and agricultural economies. In all cases, the first dimension identified by this approach replicates standard one-dimensional estimates and captures success in cash economies. The novel dimensions we identify reflect success in different agricultural sectors and are independently associated with key benchmarks of food security and human growth, such as adult body mass index and child height. The multidimensional models of wealth we describe here provide new opportunities for examining the causes and consequences of wealth inequality that go beyond success in cash economies, for tracing the emergence of hybrid pathways to prosperity, and for assessing how these different pathways to economic success carry different health risks and social opportunities.