A comparison of experience-dependent locomotory behaviors and biogenic amine neurons in nematode relatives of Caenorhabditis elegans

Background: Survival of an animal depends on its ability to match its responses to environmental conditions. To generate an optimal behavioral output, the nervous system must process sensory information and generate a directed motor output in response to stimuli. The nervous system should also store information about experiences to use in the future. The diverse group of free-living nematodes provides an excellent system to study macro- and microevolution of molecular, morphological and behavioral character states associated with such nervous system function. We asked whether an adaptive behavior would vary among bacterivorous nematodes and whether differences in the neurotransmitter systems known to regulate the behavior in one species would reflect differences seen in the adaptive behavior among those species. Caenorhabditis elegans worms slow in the presence of food; this 'basal' slowing is triggered by dopaminergic mechanosensory neurons that detect bacteria. Starved worms slow more dramatically; this 'enhanced' slowing is regulated by serotonin. Results: We examined seven nematode species with known phylogenetic relationship to C. elegans for locomotory behaviors modulated by food (E. coli), and by the worm's recent history of feeding (being well-fed or starved). We found that locomotory behavior in some species was modulated by food and recent feeding experience in a manner similar to C. elegans, but not all the species tested exhibited these food-modulated behaviors. We also found that some worms had different responses to bacteria other than E. coli. Using histochemical and immunological staining, we found that dopaminergic neurons were very similar among all species. For instance, we saw likely homologs of four bilateral pairs of dopaminergic cephalic and deirid neurons known from C. elegans in all seven species examined. In contrast, there was greater variation in the patterns of serotonergic neurons. The presence of presumptive homologs of dopaminergic and serotonergic neurons in a given species did not correlate with the observed differences in locomotory behaviors. Conclusions: This study demonstrates that behaviors can differ significantly between species that appear morphologically very similar, and therefore it is important to consider factors, such as ecology of a species in the wild, when formulating hypotheses about the adaptive significance of a behavior. Our results suggest that evolutionary changes in locomotory behaviors are less likely to be caused by changes in neurotransmitter expression of neurons. Such changes could be caused either by subtle changes in neural circuitry or in the function of the signal transduction pathways mediating these behaviors

Heritable variation in stomatal responses to elevated CO2 in wild radish, Raphanus raphanistrum (Brassicaceae)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142049/1/ajb20253.pd

Generation Z, Learning Preferences, and Technology: An Academic Technology Framework Based on Enterprise Architecture

This work provides an overview of Generation X, Y (Millennials), and Z and their characteristics in academia. We present the ways that mobile technology is infused into their lifestyle. We reference how Generation Y and Z in particular expect technology to be integrated into their educational experience, as well as how it helps faculty to facilitate both synchronous and asynchronous learning. Furthermore, an overview is provided of how technology currently contributes to learning and provides a framework for how educators can better engage current students. The conceptual academic technology framework (ATF) put forth in this work will provide an immediate impact in several key areas. This framework enhances structure during course design, which may be based directly on learning outcomes and department/school objectives. It will also directly improve consistency in faculty/student communication by closely monitoring how changes in communication methods have evolved. Finally, we describe how to integrate technology in a meaningful way, in a manner that does not distract students while preparing them for careers in business

Response and Resistance to Paradox-Breaking BRAF Inhibitor in Melanomas

FDA-approved BRAF inhibitors produce high response rates and improve overall survival in patients with BRAF V600E/K-mutant melanoma, but are linked to pathologies associated with paradoxical ERK1/2 activation in wild-type BRAF cells. To overcome this limitation, a next-generation paradox-breaking RAF inhibitor (PLX8394) has been designed. Here, we show that by using a quantitative reporter assay, PLX8394 rapidly suppressed ERK1/2 reporter activity and growth of mutant BRAF melanoma xenografts. Ex vivo treatment of xenografts and use of a patient-derived explant system (PDeX) revealed that PLX8394 suppressed ERK1/2 signaling and elicited apoptosis more effectively than the FDA-approved BRAF inhibitor, vemurafenib. Furthermore, PLX8394 was efficacious against vemurafenibresistant BRAF splice variant-expressing tumors and reduced splice variant homodimerization. Importantly, PLX8394 did not induce paradoxical activation of ERK1/2 in wild-type BRAF cell lines or PDeX. Continued in vivo dosing of xenografts with PLX8394 led to the development of acquired resistance via ERK1/2 reactivation through heterogeneous mechanisms; however, resistant cells were found to have differential sensitivity to ERK1/2 inhibitor. These findings highlight the efficacy of a paradox-breaking selective BRAF inhibitor and the use of PDeX system to test the efficacy of therapeutic agents. © 2017 American Association for Cancer Research

An efficacy trial of an electronic health record-based strategy to inform patients on safe medication use: The role of written and spoken communication

We tested the feasibility and efficacy of an electronic health record (EHR) strategy that automated the delivery of print medication information at the time of prescribing

Genotype-specific effects of elevated CO 2 on fecundity in wild radish ( Raphanus raphanistrum )

Rising atmospheric CO 2 may lead to natural selection for genotypes that exhibit greater fitness under these conditions. The potential for such evolutionary change will depend on the extent of within-population genetic variation in CO 2 responses of wild species. We tested for heritable variation in CO 2 -dependent life history responses in a weedy, cosmopolitan annual, Raphanus raphanistrum . Progeny from five paternal families were grown at ambient and twice ambient CO 2 using outdoor open-top chambers (160 plants per CO 2 treatment). Elevated CO 2 stimulated net assimilation rates, especially in plants that had begun flowering. Across paternal families, elevated CO 2 led to significant increases in flower and seed production (by 22% and 13% respectively), but no effect was seen on time to bolting, leaf area at bolting, fruit set, or number of seeds per fruit. Paternal families differed in their response to the CO 2 treatment: in three families there were no significant CO 2 effects, while in one family lifetime fecundity increased by >50%. These genotype-specific effects altered fitness rankings among the five paternal families. Although we did not detect a significant genotype x CO 2 interaction, our results provide evidence for heritable responses to elevated CO 2 . In a subset of plants, we found that the magnitude of CO 2 effects on fecundity was also influenced by soil fertility.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47801/1/442_2004_Article_BF00317913.pd

Power, Validity, Bias and Robustness of Family-based Association Analysis Methods in the Presence of Linkage for Late Onset Diseases

This simulation-based report compares the performance of five methods of association analysis in the presence of linkage using extended sibships: the Family-Based Association Test (FBAT), Empirical Variance FBAT (EV-FBAT), Conditional Logistic Regression (CLR), Robust CLR (R-CLR) and Sibship Disequilibrium Test (SDT). The two tests accounting for residual familial correlation (EV-FBAT and R-CLR) and the model-free SDT showed correct test size in all simulated designs, while FBAT and CLR were only valid for small effect sizes. SDT had the lowest power, while CLR had the highest power, generally similar to FBAT and the robust variance analogues. The power of all model-dependent tests dropped when the model was misspecified, although often not substantially. Estimates of genetic effect with CLR and R-CLR were unbiased when the disease locus was analysed but biased when a nearby marker was analysed. This study demonstrates that the genetic effect does not need to be extreme to invalidate tests that ignore familial correlation and confirms that analogous methods using robust variance estimation provide a valid alternative at little cost to power. Overall R-CLR is the best-performing method among these alternatives for the analysis of extended sibship data

Model-based Robotic Dynamic Motion Control for the Robonaut 2 Humanoid Robot

Robonaut 2 (R2), an upper-body dexterous humanoid robot, has been undergoing experimental trials on board the International Space Station (ISS) for more than a year. R2 will soon be upgraded with two climbing appendages, or legs, as well as a new integrated model-based control system. This control system satisfies two important requirements; first, that the robot can allow humans to enter its workspace during operation and second, that the robot can move its large inertia with enough precision to attach to handrails and seat track while climbing around the ISS. This is achieved by a novel control architecture that features an embedded impedance control law on the motor drivers called Multi-Loop control which is tightly interfaced with a kinematic and dynamic coordinated control system nicknamed RoboDyn that resides on centralized processors. This paper presents the integrated control algorithm as well as several test results that illustrate R2's safety features and performance

Impact of anaemia at discharge following colorectal cancer surgery

Objectives: Preoperative anaemia is common in patients with colorectal cancer and increasingly optimised prior to surgery. Comparably little attention is given to the prevalence and consequences of postoperative anaemia. We aimed to investigate the frequency and short- or long-term impact of anaemia at discharge following colorectal cancer resection. Methods: A dedicated, prospectively populated database of elective laparoscopic colorectal cancer procedures undertaken with curative intent within a fully implemented ERAS protocol was utilised. The primary endpoint was anaemia at time of discharge (haemoglobin (Hb) < 120 g/L for women and < 135 g/L for men). Patient demographics, tumour characteristics, operative details and postoperative outcomes were captured. Median follow-up was 61 months with overall survival calculated with the Kaplan-Meier log rank method and Cox proportional hazard regression based on anaemia at time of hospital discharge. Results: A total of 532 patients with median 61-month follow-up were included. 46.4% were anaemic preoperatively (cohort mean Hb 129.4 g/L ± 18.7). Median surgical blood loss was 100 mL (IQR 0–200 mL). Upon discharge, most patients were anaemic (76.6%, Hb 116.3 g/L ± 14, mean 19 g/L ± 11 below lower limit of normal, p < 0.001). 16.7% experienced postoperative complications which were associated with lower discharge Hb (112 g/L ± 12 vs. 117 g/L ± 14, p = 0.001). Patients discharged anaemic had longer hospital stays (7 [5–11] vs. 6 [5–8], p = 0.037). Anaemia at discharge was independently associated with reduced overall survival (82% vs. 70%, p = 0.018; HR 1.6 (95% CI 1.04–2.5), p = 0.034). Conclusion: Anaemia at time of discharge following elective laparoscopic colorectal cancer surgery and ERAS care is common with associated negative impacts upon short-term clinical outcomes and long-term overall survival