Watershed Learning Activity: Coming to Terms with Geographic Scale

Want better dialogue in your watershed group? Proles may result from participants\u27 misunderstanding of geographic scale. The Watershed Learning Activity can foster an understanding of the importance of geographic scale through group-based experiential learning that combines aerial photography and conceptual change theory. Try it at your next watershed meeting

The Development and Validation of the Diversity Dispositions Index

The population of the U.S. is becoming increasingly more diverse. Yet, administrators and teachers in the U.S. are predominantly European Americans from middle-class backgrounds who speak only English. Many of their students are racial and ethnic minorities, live in poverty, and speak a first language other than English (Banks et aI., 2005, p. 237). The No Child Left Behind Act signed into law in2002 requires school districts to hire highly qualified teachers who possess the necessary dispositions to ensure that all children learn (Center on Education Policy, 2002). School administrators and teachers must understand students\u27 backgrounds and experiences, and they must possess the necessary dispositions to work with students from diverse backgrounds (Villegas & Lucas, 2007)

Leu8 and Pro8 oxytocin agonism differs across human, macaque, and marmoset vasopressin 1a receptors

Oxytocin (OXT) is an important neuromodulator of social behaviors via activation of both oxytocin receptors (OXTR) and vasopressin (AVP) 1a receptors (AVPR1a). Marmosets are neotropical primates with a modified OXT ligand (Pro8-OXT), and this ligand shows significant coevolution with traits including social monogamy and litter size. Pro8-OXT produces more potent and efficacious responses at primate OXTR and stronger behavioral effects than the consensus mammalian OXT ligand (Leu8-OXT). Here, we tested whether OXT/AVP ligands show differential levels of crosstalk at primate AVPR1a. We measured binding affinities and Ca2+ signaling responses of AVP, Pro8-OXT and Leu8-OXT at human, macaque, and marmoset AVPR1a. We found that AVP binds with higher affinity than OXT across AVPR1a, and marmoset AVPR1a show a 10-fold lower OXT binding affinity compared to human and macaque AVPR1a. Both Leu8-OXT and Pro8-OXT produce a less efficacious response than AVP at human AVPR1a and higher efficacious response than AVP at marmoset AVPR1a. These data suggest that OXT might partially antagonize endogenous human AVPR1a signaling and enhance marmoset AVPR1a signaling. These findings aid in further understanding inconsistencies observed following systemic intranasal administration of OXT and provide important insights into taxon-specific differences in nonapeptide ligand/receptor coevolution and behavior

Processes, Roles and Their Interactions

Taking an interaction network oriented perspective in informatics raises the challenge to describe deterministic finite systems which take part in networks of nondeterministic interactions. The traditional approach to describe processes as stepwise executable activities which are not based on the ordinarily nondeterministic interaction shows strong centralization tendencies. As suggested in this article, viewing processes and their interactions as complementary can circumvent these centralization tendencies. The description of both, processes and their interactions is based on the same building blocks, namely finite input output automata (or transducers). Processes are viewed as finite systems that take part in multiple, ordinarily nondeterministic interactions. The interactions between processes are described as protocols. The effects of communication between processes as well as the necessary coordination of different interactions within a processes are both based on the restriction of the transition relation of product automata. The channel based outer coupling represents the causal relation between the output and the input of different systems. The coordination condition based inner coupling represents the causal relation between the input and output of a single system. All steps are illustrated with the example of a network of resource administration processes which is supposed to provide requesting user processes exclusive access to a single resource.Comment: In Proceedings IWIGP 2012, arXiv:1202.422

Exploring Stakeholder Consensus for Multiple Outcomes in Agriculture: An Iowa Case Study

Extensive row-crop agricultural production systems dominant in the United States Corn Belt are designed to produce high yields of a small number of commodities at low production costs. While remarkably valuable, this model of agriculture is directly and indirectly associated with significant externalized public costs and questions about its long-term viability. Agro-environmental conservation policy in the United States has failed to deliver desired environmental outcomes at broad scales, in part, because policy is supply-oriented with scaled financial and technical incentives aimed at the interests of individual farm managers. Understanding broader stakeholder demand relative to agro-ecosystem outcomes is fundamental to modifying policy toward outcomes. Failed collective policy and management, often indicates failed consensus among stakeholders whose responsibilities are to provide guidance for achieving outcomes. We used a Delphi approach with representatives from Iowa-based agricultural and/or environmental policy, outreach, and industry organizations to explore whether or not consensus may exist regarding desired agricultural outcomes and if so, modes of provision. Through three iterative surveys, we found consensus regarding the array of ecosystem outcomes believed possible within the Iowa agricultural economy. However, when agricultural interests were sorted, a divide emerged between stakeholders who emphasize production agriculture and those who favor a more multi-outcome oriented agriculture that emphasizes multiple ecosystem services. Nevertheless, study participants identified several key ecosystem outcomes, and methods for providing them that are strongly compatible with and support private commodity driven land use while mitigating costly public externalities. A broad and simple six-point framework emerged from our data to contextualize questions and discussions of agricultural land-use management among stakeholders. This framework includes people, their expectations and values, land, management, and ecosystem processes in addition to ecosystem services. Broadening and bounding discourse in these ways may facilitate a shared appreciation of human-nature interconnections and more progressive policy reform that facilitates understanding of land-use decision making within agricultural contexts in ways that benefit all stakeholders

Agonist-Specific Desensitization of PGE2-Stimulated cAMP Signaling due to upregulated Phosphodiesterase Expression in Human Lung Fibroblasts

Pulmonary fibrosis is characterized by fibroblasts persisting in an activated form, producing excessive fibrous material that destroys alveolar structure. The second messenger molecule cyclic 3′,5′-adenosine monophosphate (cAMP) has antifibrotic properties, and prostaglandin E2 (PGE2) can stimulate cAMP production through prostaglandin E (EP)2 and EP4 receptors. Although EP receptors are attractive therapeutic targets, the effects of long-term exposure to PGE2 have not been characterized. To determine the effects of long-term exposure of lung fibroblasts to PGE2, human fetal lung (HFL)-1 cells were treated for 24 h with 100 nM PGE2 or other cAMP-elevating agents. cAMP levels stimulated by acute exposure to PGE2 were measured using a fluorescent biosensor. Pretreatment for 24 h with PGE2 shifted the concentration-response curve to PGE2 rightward by approximately 22-fold but did not affect responses to the beta-adrenoceptor agonist isoproterenol. Neither isoproterenol nor forskolin pretreatment altered PGE2 responses, implying that other cAMP-elevating agents do not induce desensitization. Use of EP2- and EP4-selective agonists and antagonists suggested that PGE2-stimulated cAMP responses in HFL-1 cells are mediated by EP2 receptors. EP2 receptors are resistant to classical mechanisms of agonist-specific receptor desensitization, so we hypothesized that increased PDE activity mediates the loss of signaling after PGE2 pretreatment. PGE2 treatment upregulated messenger RNA for PDE3A, PDE3B, PDE4B, and PDE4D and increased overall PDE activity. The PDE4 inhibitor rolipram partially reversed PGE2- mediated desensitization and PDE4 activity was increased, but rolipram did not alter responses to isoproterenol. The PDE3 inhibitor cilostazol had minimal effect. These results show that long-term exposure to PGE2 causes agonist-specific desensitization of EP2 receptor-stimulated cAMP signaling through the increased expression of PDE isozymes, most likely of the PDE4 family

ATM Limits Incorrect End Utilization during Non-Homologous End Joining of Multiple Chromosome Breaks

Chromosome rearrangements can form when incorrect ends are matched during end joining (EJ) repair of multiple chromosomal double-strand breaks (DSBs). We tested whether the ATM kinase limits chromosome rearrangements via suppressing incorrect end utilization during EJ repair of multiple DSBs. For this, we developed a system for monitoring EJ of two tandem DSBs that can be repaired using correct ends (Proximal-EJ) or incorrect ends (Distal-EJ, which causes loss of the DNA between the DSBs). In this system, two DSBs are induced in a chromosomal reporter by the meganuclease I-SceI. These DSBs are processed into non-cohesive ends by the exonuclease Trex2, which leads to the formation of I-SceI–resistant EJ products during both Proximal-EJ and Distal-EJ. Using this method, we find that genetic or chemical disruption of ATM causes a substantial increase in Distal-EJ, but not Proximal-EJ. We also find that the increase in Distal-EJ caused by ATM disruption is dependent on classical non-homologous end joining (c-NHEJ) factors, specifically DNA-PKcs, Xrcc4, and XLF. We present evidence that Nbs1-deficiency also causes elevated Distal-EJ, but not Proximal-EJ, to a similar degree as ATM-deficiency. In addition, to evaluate the roles of these factors on end processing, we examined Distal-EJ repair junctions. We found that ATM and Xrcc4 limit the length of deletions, whereas Nbs1 and DNA-PKcs promote short deletions. Thus, the regulation of end processing appears distinct from that of end utilization. In summary, we suggest that ATM is important to limit incorrect end utilization during c-NHEJ

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe