Trade Blocs, Interstate Conflict, and the Collective Impact of Economic Integration

Economic integration agreements – also called preferential trade agreements or regional trade agreements – have dramatically expanded in scope since World War II. While the proximate goal of economic integration is to increase commercial exchange between member states, there are strong reasons to believe integration influences relations across economic agreements as well. I argue that economic agreements foster enclaves of regional interdependence at the expense of multilateral, global interdependence. As a result, highly central economic agreements are partially insulated from the ill-effects of militarized conflict with other agreement areas. Furthermore, the coveted markets of highly central trade blocs afford them a degree of economic leverage that increases the effectiveness of non-violent conflict resolution mechanisms. Ultimately, these dynamics suggest highly central agreements will tend to engage in conflict with other central agreements due to the mutual isolation of said agreements. Relations between central and marginalized agreements, however, will be more peaceful given the latter’s dependence on access to central agreement markets. Using eigenvector centrality scores as my primary measure of agreement centrality, I test my theory using a large-N statistical analysis. I ultimately find support for the notion that dyads with more central agreements are more conflict prone other types of dyads

Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, similar to 80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (similar to 90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu

A Course-Based Research Experience: How Benefits Change with Increased Investment in Instructional Time

There is widespread agreement that science, technology, engineering, and mathematics programs should provide undergraduates with research experience. Practical issues and limited resources, however, make this a challenge. We have developed a bioinformatics project that provides a course-based research experience for students at a diverse group of schools and offers the opportunity to tailor this experience to local curriculum and institution-specific student needs. We assessed both attitude and knowledge gains, looking for insights into how students respond given this wide range of curricular and institutional variables. While different approaches all appear to result in learning gains, we find that a significant investment of course time is required to enable students to show gains commensurate to a summer research experience. An alumni survey revealed that time spent on a research project is also a significant factor in the value former students assign to the experience one or more years later. We conclude: 1) implementation of a bioinformatics project within the biology curriculum provides a mechanism for successfully engaging large numbers of students in undergraduate research; 2) benefits to students are achievable at a wide variety of academic institutions; and 3) successful implementation of course-based research experiences requires significant investment of instructional time for students to gain full benefit

Speed and Surface Speed and Magnitude of Knee Adduction

Frontal plane knee biomechanics, in particular speed and magnitude of knee adduction motion, are implicated in knee osteoarthritis development. Although individuals are between 50% to 90% more likely to develop knee osteoarthritis after anterior cruciate ligament reconstruction (ACL-R), it is unknown if ACL-R individuals exhibit knee adduction biomechanics related to OA development. This study sought to quantify speed and magnitude of knee adduction for knee OA and ACL-R individuals. We hypothesize that OA will exhibit larger, faster knee adduction biomechanics than ACL-R, which will increase at great walk speed and over a challenging surface. Six individuals with ACL-R and 8 individuals with knee OA had knee adduction quantified as they walked 1.3 m/s and at a self-selected speed over a flat and an uneven surface. Peak of stance, and average and maximum velocity of knee adduction joint angle and moment between heel strike and peak of stance were submitted to repeated measures ANOVA to compare main and interaction effects between group, speed and surface. There was a walk speed by group interaction for peak knee adduction moment (p = 0.048). Walk speed impacted maximum knee adduction joint angle (p=0.004) and moment velocity (p=0.041), while surface impacted peak knee adduction joint angle (p=0.035) and maximum knee adduction joint moment velocity (p=0.007). In partial agreement with our hypothesis, speed and magnitude knee adduction biomechanics increased with walk speed and surface, but OA did not consistently exhibit larger knee adduction biomechanics than ACL-R

Impact of Knee Injury and Disease on Frontal Plane Knee Biomechanics During Walk on Uneven Surfaces

Frontal plane knee biomechanics, in particular speed and magnitude of knee adduction motion, are implicated in knee osteoarthritis development. Although individuals are between 50% to 90% more likely to develop knee osteoarthritis after anterior cruciate ligament reconstruction (ACL-R), it is unknown if ACL-R individuals exhibit knee adduction biomechanics related to OA development. This study sought to quantify speed and magnitude of knee adduction for knee OA and ACL-R individuals. We hypothesize that OA will exhibit larger, faster knee adduction biomechanics than ACL-R, which will increase at great walk speed and over a challenging surface. Six individuals with ACL-R and 8 individuals with knee OA had knee adduction quantified as they walked 1.3 m/s and at a self-selected speed over a flat and an uneven surface. Peak of stance, and average and maximum velocity of knee adduction joint angle and moment between heel strike and peak of stance were submitted to repeated measures ANOVA to compare main and interaction effects between group, speed and surface. There was a walk speed by group interaction for peak knee adduction moment (p = 0.048). Walk speed impacted maximum knee adduction joint angle (p=0.004) and moment velocity (p=0.041), while surface impacted peak knee adduction joint angle (p=0.035) and maximum knee adduction joint moment velocity (p=0.007). In partial agreement with our hypothesis, speed and magnitude knee adduction biomechanics increased with walk speed and surface, but OA did not consistently exhibit larger knee adduction biomechanics than ACL-R

Governance through Shame and Aspiration: Index Creation and Corporate Behavior in Japan

We study how a stock index can affect corporate behavior by serving as a source of prestige. After decades of low corporate profitability in Japan, the JPX-Nikkei400 index was introduced in 2014. The index selected 400 large and liquid firms deemed to be best-performing in terms of profitability annually; membership was considered highly prestigious. We document that index-inclusion incentives led firms to increase return on equity (ROE) proportionally by 35% on average, through higher margins, efficiency, or shareholder payouts, depending on where firms had “slack,” but not through changing investments or accruals. These incentives are driven by the prestige associated with the index rather than capital market benefits. Back-of-envelope estimates suggest that the index accounted for 23% of the average increase in aggregate annual earnings over our sample period and a 3% increase in aggregate market capitalization. These findings highlight a novel mechanism through which long-standing corporate behaviors can be transformed

Diverse Intestinal Bacteria Contain Putative Zwitterionic Capsular Polysaccharides with Anti-inflammatory Properties

Zwitterionic capsular polysaccharides (ZPSs) are bacterial products that modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). However, only a few diverse bacteria are known to modulate the host immune system via ZPS. We present a genomic screen for bacteria encoding ZPS molecules. We identify diverse host-associated bacteria, including commensals and pathogens with known anti-inflammatory properties, with the capacity to produce ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing bacteria induce significantly greater IL-10 production and higher proportions of Tregs than lysates from non-ZPS-encoding relatives or a commensal strain of Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was genetically disrupted. Similarly, wild-type B. cellulosilyticus DSM 14838, but not a close relative lacking a putative ZPS, attenuated experimental colitis in mice. Collectively, this screen identifies bacterial strains that may use ZPSs to interact with the host as well as those with potential probiotic properties

Serum Deprivation of Mesenchymal Stem Cells Improves Exosome Activity and Alters Lipid and Protein Composition

Exosomes can serve as delivery vehicles for advanced therapeutics. The components necessary and sufficient to support exosomal delivery have not been established. Here we connect biochemical composition and activity of exosomes to optimize exosome-mediated delivery of small interfering RNAs (siRNAs). This information is used to create effective artificial exosomes. We show that serum-deprived mesenchymal stem cells produce exosomes up to 22-fold more effective at delivering siRNAs to neurons than exosomes derived from control cells. Proteinase treatment of exosomes stops siRNA transfer, indicating that surface proteins on exosomes are involved in trafficking. Proteomic and lipidomic analyses show that exosomes derived in serum-deprived conditions are enriched in six protein pathways and one lipid class, dilysocardiolipin. Inspired by these findings, we engineer an artificial exosome, in which the incorporation of one lipid (dilysocardiolipin) and three proteins (Rab7, Desmoplakin, and AHSG) into conventional neutral liposomes produces vesicles that mimic cargo delivering activity of natural exosomes

Genome-wide association study of dental caries in the Hispanic Communities Health Study/Study of Latinos (HCHS/SOL)

Dental caries is the most common chronic disease worldwide, and exhibits profound disparities in the USA with racial and ethnic minorities experiencing disproportionate disease burden. Though heritable, the specific genes influencing risk of dental caries remain largely unknown. Therefore, we performed genome-wide association scans (GWASs) for dental caries in a population-based cohort of 12 000 Hispanic/Latino participants aged 18–74 years from the HCHS/SOL. Intra-oral examinations were used to generate two common indices of dental caries experience which were tested for association with 27.7 M genotyped or imputed single-nucleotide polymorphisms separately in the six ancestry groups. A mixed-models approach was used, which adjusted for age, sex, recruitment site, five principal components of ancestry and additional features of the sampling design. Meta-analyses were used to combine GWAS results across ancestry groups. Heritability estimates ranged from 20–53% in the six ancestry groups. The most significant association observed via meta-analysis for both phenotypes was in the region of the NAMPT gene (rs190395159; P-value = 6 × 10−10), which is involved in many biological processes including periodontal healing. Another significant association was observed for rs72626594 (P-value = 3 × 10−8) downstream of BMP7, a tooth development gene. Other associations were observed in genes lacking known or plausible roles in dental caries. In conclusion, this was the largest GWAS of dental caries, to date and was the first to target Hispanic/Latino populations. Understanding the factors influencing dental caries susceptibility may lead to improvements in prediction, prevention and disease management, which may ultimately reduce the disparities in oral health across racial, ethnic and socioeconomic strata

Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotopes

Genomic analysis of a large set of phages infecting the common hostMycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode