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1. Proteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation

Author

Valeria Lallai, TuKiet T. Lam, Rolando Garcia-Milian, Yen-Chu Chen, James P. Fowler, Letizia Manca, Daniele Piomelli, Kenneth Williams, Angus C. Nairn, and Christie D. Fowler

Subjects
cannabis, THC, extracellular vesicles, cerebrospinal fluid, proteomic, Microbiology, QR1-502
Abstract

Given the increasing use of cannabis in the US, there is an urgent need to better understand the drug’s effects on central signaling mechanisms. Extracellular vesicles (EVs) have been identified as intercellular signaling mediators that contain a variety of cargo, including proteins. Here, we examined whether the main psychoactive component in cannabis, Δ9-tetrahydrocannabinol (THC), alters EV protein signaling dynamics in the brain. We first conducted in vitro studies, which found that THC activates signaling in choroid plexus epithelial cells, resulting in transcriptional upregulation of the cannabinoid 1 receptor and immediate early gene c-fos, in addition to the release of EVs containing RNA cargo. Next, male and female rats were examined for the effects of either acute or chronic exposure to aerosolized (‘vaped’) THC on circulating brain EVs. Cerebrospinal fluid was extracted from the brain, and EVs were isolated and processed with label-free quantitative proteomic analyses via high-resolution tandem mass spectrometry. Interestingly, circulating EV-localized proteins were differentially expressed based on acute or chronic THC exposure in a sex-specific manner. Taken together, these findings reveal that THC acts in the brain to modulate circulating EV signaling, thereby providing a novel understanding of how exogenous factors can regulate intercellular communication in the brain.

Published
2024
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2. Differential Expression Patterns of Lynx Proteins and Involvement of Lynx1 in Prepulse Inhibition

Author

Yasmine Sherafat, Edison Chen, Valeria Lallai, Malia Bautista, James P. Fowler, Yen-Chu Chen, Julie Miwa, and Christie D. Fowler

Subjects
nicotinic acetylcholin receptor (nAChR), cholinergic signaling, sensory gating, learning and memory, cognitive flexibility, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Negative allosteric modulators, such as lynx1 and lynx2, directly interact with nicotinic acetylcholine receptors (nAChRs). The nAChRs are integral to cholinergic signaling in the brain and have been shown to mediate different aspects of cognitive function. Given the interaction between lynx proteins and these receptors, we examined whether these endogenous negative allosteric modulators are involved in cognitive behaviors associated with cholinergic function. We found both cell-specific and overlapping expression patterns of lynx1 and lynx2 mRNA in brain regions associated with cognition, learning, memory, and sensorimotor processing, including the prefrontal cortex (PFC), cingulate cortex, septum, hippocampus, amygdala, striatum, and pontine nuclei. Since lynx proteins are thought to play a role in conditioned associations and given the expression patterns across brain regions, we first assessed whether lynx knockout mice would differ in a cognitive flexibility task. We found no deficits in reversal learning in either the lynx1–/– or lynx2–/– knockout mice. Thereafter, sensorimotor gating was examined with the prepulse inhibition (PPI) assessment. Interestingly, we found that both male and female lynx1–/– mice exhibited a deficit in the PPI behavioral response. Given the comparable expression of lynx2 in regions involved in sensorimotor gating, we then examined whether removal of the lynx2 protein would lead to similar behavioral effects. Unexpectedly, we found that while male lynx2–/– mice exhibited a decrease in the baseline startle response, no differences were found in sensorimotor gating for either male or female lynx2–/– mice. Taken together, these studies provide insight into the expression patterns of lynx1 and lynx2 across multiple brain regions and illustrate the modulatory effects of the lynx1 protein in sensorimotor gating.

Published
2021
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3. Material selection of intraoral stents for head and neck cancer patients undergoing radiation therapy: A Multi-criteria, Multi-physics design approach

Author

Negin Kazemian, James D. Fowler, Faizan Muhammad Khalid, Kirsty Milligan, Sahar Alousi, Sebastian Sabry, Hilary Pada, Cynthia Araujo, Andrew Jirasek, Abbas S. Milani, and Sepideh Pakpour

Subjects
Head and Neck Cancer, Radiotherapy, Intraoral stents, Backscatter radiation, Multicriteria decision making, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

Radiation therapy (RT) plays a key role in curative-intent treatments for head and neck cancer (HNC). Despite the advancements in RT, high doses of radiation can disrupt the oral cavity homeostasis and result in undesired reactions. Thus, intraoral stents (IOSs) are utilized for patients during RT to prevent unnecessary irradiation to surrounding tissues. However, no studies have compared commonly used IOS materials and their potential toxicity. Therefore, the objective of this study is to perform a detailed assessment of ten IOS materials in order to select the top-ranked material for HNC patients undergoing RT. Thus, beam attenuation measurements, and Raman spectroscopy and mechanical testing were conducted pre- and post-artificial saliva, RT, and artificial saliva and RT exposure. Finally, through a multi-criteria decision making (MCDM) analysis using Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS), our study demonstrated that Ethylene Vinyl Acetate (EVA) was the top-ranked material. The saliva samples were also tested via nuclear magnetic resonance (NMR) spectroscopy, which showed no leaching of irradiated materials. Taken together, these data suggest that EVA is an appropriate IOS material that can be utilized during RT to reduce significant morbidity for HNC patients and improve their quality of life.

Published
2023
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4. The Structure of Negative Social Ties in Rural Village Networks

Author

Alexander Isakov, James H. Fowler, Edoardo M. Airoldi, and Nicholas A. Christakis

Subjects
Negative ties, Antagonistic Ties, Animosity, Enemies, Social Networks, Network Structure, Sociology (General), HM401-1281
Abstract

Negative (antagonistic) connections have been of longstanding theoretical importance for social structure. In a population of 24,696 adults interacting face to face within 176 isolated villages in western Honduras, we measured all connections that were present, amounting to 105,175 positive and 16,448 negative ties. Here, we show that negative and positive ties exhibit many of the same structural characteristics. We then develop a complete taxonomy of all 138 possible triads of two-type relationships. Consistent with balance theory, we find that antagonists of friends and friends of antagonists tend to be antagonists; but, in an important empirical refutation of balance theory, we find that antagonists of antagonists also tend to be antagonists, not friends. Finally, villages with comparable levels of animosity tend to be geographically proximate. Similar processes, involving social contact, give rise to both positive and negative social ties in rural villages, and negative ties play an important role in social structure.

Published
2019
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5. Stay-at-home orders associate with subsequent decreases in COVID-19 cases and fatalities in the United States

Author

James H. Fowler, Seth J. Hill, Remy Levin, and Nick Obradovich

Subjects
Medicine, Science
Abstract

Governments issue “stay-at-home” orders to reduce the spread of contagious diseases, but the magnitude of such orders’ effectiveness remains uncertain. In the United States these orders were not coordinated at the national level during the coronavirus disease 2019 (COVID-19) pandemic, which creates an opportunity to use spatial and temporal variation to measure the policies’ effect. Here, we combine data on the timing of stay-at-home orders with daily confirmed COVID-19 cases and fatalities at the county level during the first seven weeks of the outbreak in the United States. We estimate the association between stay-at-home orders and alterations in COVID-19 cases and fatalities using a difference-in-differences design that accounts for unmeasured local variation in factors like health systems and demographics and for unmeasured temporal variation in factors like national mitigation actions and access to tests. Compared to counties that did not implement stay-at-home orders, the results show that the orders are associated with a 30.2 percent (11.0 to 45.2) average reduction in weekly incident cases after one week, a 40.0 percent (23.4 to 53.0) reduction after two weeks, and a 48.6 percent (31.1 to 61.7) reduction after three weeks. Stay-at-home orders are also associated with a 59.8 percent (18.3 to 80.2) average reduction in weekly fatalities after three weeks. These results suggest that stay-at-home orders might have reduced confirmed cases by 390,000 (170,000 to 680,000) and fatalities by 41,000 (27,000 to 59,000) within the first three weeks in localities that implemented stay-at-home orders.

Published
2021

6. Spatiotemporal network structure among 'friends of friends' reveals contagious disease process.

Author

Carmel Witte, Laura L Hungerford, Bruce A Rideout, Rebecca Papendick, and James H Fowler

Subjects
Medicine, Science
Abstract

Disease transmission can be identified in a social network from the structural patterns of contact. However, it is difficult to separate contagious processes from those driven by homophily, and multiple pathways of transmission or inexact information on the timing of infection can obscure the detection of true transmission events. Here, we analyze the dynamic social network of a large, and near-complete population of 16,430 zoo birds tracked daily over 22 years to test a novel "friends-of-friends" strategy for detecting contagion in a social network. The results show that cases of avian mycobacteriosis were significantly clustered among pairs of birds that had been in direct contact. However, since these clusters might result due to correlated traits or a shared environment, we also analyzed pairs of birds that had never been in direct contact but were indirectly connected in the network via other birds. The disease was also significantly clustered among these friends of friends and a reverse-time placebo test shows that homophily could not be causing the clustering. These results provide empirical evidence that at least some avian mycobacteriosis infections are transmitted between birds, and provide new methods for detecting contagious processes in large-scale global network structures with indirect contacts, even when transmission pathways, timing of cases, or etiologic agents are unknown.

Published
2020
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7. Physical Activity and Insulin Resistance in 6,500 NHANES Adults: The Role of Abdominal Obesity

Author

James R. Fowler, Larry A. Tucker, Bruce W. Bailey, and James D. LeCheminant

Subjects
Internal medicine, RC31-1245
Abstract

This cross-sectional investigation studied differences in insulin resistance across levels of physical activity in 6,500 US adults who were randomly selected as part of the National Health and Nutrition Examination Survey (NHANES). Another important objective was to determine the influence of abdominal obesity on the physical activity and insulin resistance relationship. MET-minutes were utilized to quantify total activity based on participation in 48 different physical activities. Two strategies were employed to categorize levels of physical activity: one was based on relative MET-minutes (quartiles), and the other approach was based on the US physical activity guidelines. Insulin resistance was indexed using the homeostatic model assessment (HOMA). Abdominal obesity was indexed using waist circumference. Effect modification was tested by dividing waist circumferences into sex-specific quartiles and then evaluating the relationship between physical activity and HOMA-IR within each quartile separately. Results showed that relative physical activity level was associated with HOMA-IR after controlling for demographic and demographic and lifestyle covariates (F = 11.5, P

Published
2020
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8. International chicken trade and increased risk for introducing or reintroducing highly pathogenic avian influenza A (H5N1) to uninfected countries

Author

Jennifer M. Radin, Richard A. Shaffer, Suzanne P. Lindsay, Maria Rosario G. Araneta, Rema Raman, and James H. Fowler

Subjects
Highly pathogenic avian influenza A (H5N1), Poultry trade, Transmission model, Zoonotic disease, Infectious and parasitic diseases, RC109-216
Abstract

Every year billions of chickens are shipped thousands of miles around the globe in order to meet the ever increasing demands for this cheap and nutritious protein source. Unfortunately, transporting chickens internationally can also increase the chance for introducing zoonotic viruses, such as highly pathogenic avian influenza A (H5N1) to new countries. Our study used a retrospective analysis of poultry trading data from 2003 through 2011 to assess the risk of H5N1 poultry infection in an importing country. We found that the risk of infection in an importing country increased by a factor of 1.3 (95% CI: 1.1–1.5) for every 10-fold increase in live chickens imported from countries experiencing at least one H5N1 poultry case during that year. These results suggest that the risk in a particular country can be significantly reduced if imports from countries experiencing an outbreak are decreased during the year of infection or if biosecurity measures such as screening, vaccination, and infection control practices are increased. These findings show that limiting trade of live chickens or increasing infection control practices during contagious periods may be an important step in reducing the spread of H5N1 and other emerging avian influenza viruses.

Published
2017
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9. Detecting emotional contagion in massive social networks.

Author

Lorenzo Coviello, Yunkyu Sohn, Adam D I Kramer, Cameron Marlow, Massimo Franceschetti, Nicholas A Christakis, and James H Fowler

Subjects
Medicine, Science
Abstract

Happiness and other emotions spread between people in direct contact, but it is unclear whether massive online social networks also contribute to this spread. Here, we elaborate a novel method for measuring the contagion of emotional expression. With data from millions of Facebook users, we show that rainfall directly influences the emotional content of their status messages, and it also affects the status messages of friends in other cities who are not experiencing rainfall. For every one person affected directly, rainfall alters the emotional expression of about one to two other people, suggesting that online social networks may magnify the intensity of global emotional synchrony.

Published
2014
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10. Nicotine e‐cigarette vapor inhalation and self‐administration in a rodent model: Sex‐ and nicotine delivery‐specific effects on metabolism and behavior

Author

Yen-Chu Chen, James P. Fowler, Eashan R Kotha, Christie D. Fowler, Angelique N. Cortez, Mikayla M Roybal, Andres Staben, and Valeria Lallai

Subjects
Male, Nicotine, Metabolite, Drug-Seeking Behavior, Medicine (miscellaneous), Self Administration, Electronic Nicotine Delivery Systems, Pharmacology, Article, 03 medical and health sciences, chemistry.chemical_compound, Sex Factors, 0302 clinical medicine, Neurochemical, Animals, Medicine, Rats, Wistar, Cotinine, Inhalation, business.industry, Rodent model, Metabolism, Rats, 030227 psychiatry, Psychiatry and Mental health, chemistry, E-Cigarette Vapor, Female, Self-administration, business, Locomotion, 030217 neurology & neurosurgery, medicine.drug
Abstract

E-cigarettes, which deliver vaporized nicotine, have dramatically risen in popularity in recent years, despite many unanswered questions about safety, efficacy in reducing dependence, and overall impact on public health. Other factors, such as sex, also play an important role in determining behavioral and neurochemical responses to drugs of abuse. In these studies, we sought to develop a protocol for vaporized e-cigarette nicotine self-administration in rats, as a foundation to better understand the differing effects of nicotine exposure routes on behavior and physiological function. We report a novel method that elicits robust nicotine vapor self-administration in male and female rats. Our findings indicate that 5 mg/ml nicotine vape solution provides a high level of consistency in lever-pressing behavior for both males and females. Moreover, in male rats, we find that such e-cigarette nicotine vapor induces similar blood levels of nicotine’s main metabolite, cotinine, as that found with intravenous nicotine self-administration. Therefore, the breathing pattern during vapor exposure in males leads to similar levels of titrated nicotine intake as with intravenous nicotine self-administration. Interestingly, a differential effect was found in the females, in which the same conditions of vapor exposure led to decreased cotinine levels with vapor compared to intravenous self-administration. Finally, differences in nicotine-mediated locomotion provide further support of the physiological effects of e-cigarette vapor inhalation. Taken together, our findings reveal important sex differences in nicotine intake based on the route of exposure, and we further establish a protocol for nicotine vapor self-administration in rats.

Published
2021

11. Red brain, blue brain: evaluative processes differ in Democrats and Republicans.

Author

Darren Schreiber, Greg Fonzo, Alan N Simmons, Christopher T Dawes, Taru Flagan, James H Fowler, and Martin P Paulus

Subjects
Medicine, Science
Abstract

Liberals and conservatives exhibit different cognitive styles and converging lines of evidence suggest that biology influences differences in their political attitudes and beliefs. In particular, a recent study of young adults suggests that liberals and conservatives have significantly different brain structure, with liberals showing increased gray matter volume in the anterior cingulate cortex, and conservatives showing increased gray matter volume in the in the amygdala. Here, we explore differences in brain function in liberals and conservatives by matching publicly-available voter records to 82 subjects who performed a risk-taking task during functional imaging. Although the risk-taking behavior of Democrats (liberals) and Republicans (conservatives) did not differ, their brain activity did. Democrats showed significantly greater activity in the left insula, while Republicans showed significantly greater activity in the right amygdala. In fact, a two parameter model of partisanship based on amygdala and insula activations yields a better fitting model of partisanship than a well-established model based on parental socialization of party identification long thought to be one of the core findings of political science. These results suggest that liberals and conservatives engage different cognitive processes when they think about risk, and they support recent evidence that conservatives show greater sensitivity to threatening stimuli.

Published
2013
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12. Emotion regulation as the foundation of political attitudes: does reappraisal decrease support for conservative policies?

Author

Jooa Julia Lee, Yunkyu Sohn, and James H Fowler

Subjects
Medicine, Science
Abstract

Cognitive scientists, behavior geneticists, and political scientists have identified several ways in which emotions influence political attitudes, and psychologists have shown that emotion regulation can have an important causal effect on physiology, cognition, and subjective experience. However, no work to date explores the possibility that emotion regulation may shape political ideology and attitudes toward policies. Here, we conduct four studies that investigate the role of a particular emotion regulation strategy--reappraisal in particular. Two observational studies show that individual differences in emotion regulation styles predict variation in political orientations and support for conservative policies. In the third study, we experimentally induce disgust as the target emotion to be regulated and show that use of reappraisal reduces the experience of disgust, thereby decreasing moral concerns associated with conservatism. In the final experimental study, we show that use of reappraisal successfully attenuates the relationship between trait-level disgust sensitivity and support for conservative policies. Our findings provide the first evidence of a critical link between emotion regulation and political attitudes.

Published
2013
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13. Adolescent Cannabinoid and Nicotine Exposure Differentially Alters Adult Nicotine Self-Administration in Males and Females

Author

Anna N. Pushkin, James P. Fowler, Christie D. Fowler, Angeline J. Dukes, and Valeria Lallai

Subjects
Male, Cannabinoid receptor, Mouse, medicine.medical_treatment, Original Investigations, Self Administration, Electronic Nicotine Delivery Systems, Inbred C57BL, Nicotine, Mice, 0302 clinical medicine, Psychology, media_common, Pediatric, Marketing, 0303 health sciences, biology, Substance Abuse, Reinforcement, Self-Administration, 5.1 Pharmaceuticals, Public Health and Health Services, Female, Mental health, Public Health, Development of treatments and therapeutic interventions, Self-administration, Reinforcement, Psychology, medicine.drug, Drug, Agonist, Adult, medicine.medical_specialty, Drug Abuse (NIDA Only), Adolescent, medicine.drug_class, NICOTINE EXPOSURE, media_common.quotation_subject, Clinical Sciences, Basic Behavioral and Social Science, 03 medical and health sciences, Reward, Internal medicine, Behavioral and Social Science, Tobacco, medicine, Animals, Humans, Cannabis, 030304 developmental biology, Tobacco Smoke and Health, Cannabinoid Research, Cannabinoids, Public Health, Environmental and Occupational Health, biology.organism_classification, Mice, Inbred C57BL, Endocrinology, Cannabinoid, 030217 neurology & neurosurgery
Abstract

Introduction During adolescence, exposure to nicotine or cannabis independently induces effects on neuromaturation and later cognitive function. However, the potential effect of both drugs under co-use conditions has become of increasing concern given the prevalence of e-cigarettes, legalization of cannabis, and availability of synthetic “spice” cannabinoid agonists. Aims and Methods The current studies investigated the effects of exposure to a cannabinoid receptor agonist (WIN55,212-2) and/or nicotine over a discrete time period in mid-adolescence on later intravenous nicotine self-administration in adult male and female mice. We further examined whether cannabinoid agonist administration in adulthood would alter nicotine reinforcement, with either acute or chronic pairing across 7 days. Results We found that adult males exhibited increased nicotine self-administration at a lower, rewarding nicotine dose following adolescent cannabinoid exposure, either alone or with nicotine coadministration. In contrast, adult females demonstrated an opposing effect in which adolescent cannabinoid and nicotine coexposure resulted in decreased nicotine intake compared with the nicotine only and control groups. Furthermore, after maintaining nicotine self-administration across sessions, pretreatment with a low dose of the cannabinoid agonist decreased nicotine intake in both male and female control mice, and this lowering effect was evidenced after both acute and chronic treatment. However, the cannabinoid agonist was ineffective in altering nicotine intake in mice previously exposed to nicotine, cannabinoid agonist, or both during adolescence. Conclusions These data provide evidence that adolescent drug exposure can alter later nicotine reinforcement in a sex-specific manner and can further modulate the effectiveness of interventions in reducing nicotine intake during adulthood. Implications These studies demonstrate a significant impact of nicotine, cannabinoids, or coexposure on developmental processes during adolescence. Differential effects were observed within each sex, with opposing results found for cannabinoid exposure on nicotine intake in males and females. Intriguingly, we also evidenced resistance to the lowering effects of a cannabinoid agonist on nicotine intake in adulthood based on adolescent drug exposure. Thus, these findings have important implications for our understanding of the impact of nicotine and cannabinoids (eg, Δ9-tetrahydrocannabinol (THC) and synthetic “spice” cannabinoids) during development, with further implications for the effectiveness of therapeutic interventions based on prior drug exposure in youth.

Published
2020

14. The Novel CYP2A6 Inhibitor, DLCI-1, Decreases Nicotine Self-Administration in Mice

Author

Christie D. Fowler, Jing Wang, Yen-Chu Chen, Philip Lazarus, Yasmine Sherafat, Andres Staben, Christy J. W. Watson, James P. Fowler, and Travis T. Denton

Subjects
0301 basic medicine, Male, CYP2A, Pharmacology, Inbred C57BL, Nicotine, Cytochrome P-450 CYP2A6, Mice, 0302 clinical medicine, Medicine, Pharmacology & Pharmacy, Enzyme Inhibitors, CYP2A6, Cancer, media_common, Smoking Cessation Agents, Substance Abuse, Tobacco Use Disorder, Pharmacology and Pharmaceutical Sciences, Nicotinic agonist, Liver, Behavioral Pharmacology, Molecular Medicine, Female, addiction, Self-administration, medicine.drug, Drug Abuse (NIDA Only), cytochrome P450, media_common.quotation_subject, Thiophenes, 03 medical and health sciences, Tobacco, Behavioral and Social Science, Animals, Acetylcholine receptor, Bupropion, Tobacco Smoke and Health, business.industry, Prevention, Metabolism, dependence, Abstinence, Brain Disorders, Mice, Inbred C57BL, Good Health and Well Being, 030104 developmental biology, nicotinic acetylcholine receptors, business, CYP inhibition, 030217 neurology & neurosurgery
Abstract

During tobacco and e-cigarette use, nicotine is mainly metabolized in the human liver by cytochrome P450 2A6 (CYP2A6). Given that a slower CYP2A6 metabolism has been associated with less vulnerability to develop nicotine dependence, the current studies sought to validate a novel CYP2A6 inhibitor, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), for its effects on intravenous nicotine self-administration. Male and female mice were trained to self-administer nicotine across daily sessions. Once stable responding was achieved, DLCI-1 or vehicle control was administered prior to nicotine sessions. We found that the lower 25 mg/kg and moderate 50 mg/kg doses of DLCI-1 induced a significant decrease in nicotine intake for both males and females. DLCI-1 was further shown to be more effective than a moderate 1 mg/kg dose of bupropion on reducing nicotine intake and did not exert the adverse behavioral effects found with a high 75 mg/kg dose of bupropion. Although mice treated with DLCI-1 self-administered significantly less nicotine, similar nicotine-mediated behavioral effects on locomotion were observed. Together, along with the analysis of nicotine metabolites during self-administration, these findings support the contention that blocking hepatic nicotine metabolism would allow for similar activation of nicotinic acetylcholine receptors at lower nicotine doses. Moreover, these effects of DLCI-1 were specific to nicotine self-administration, as DLCI-1 did not result in any behavioral changes during food self-administration. Taken together, these studies validate DLCI-1 as a novel compound to decrease nicotine consumption, which may thereby promote tobacco and nicotine product cessation. SIGNIFICANCE STATEMENT: Current pharmacological approaches for nicotine and tobacco cessation have only been able to achieve limited efficaciousness in promoting long-term abstinence. In this work, we characterize the effects of a novel compound, (5-(4-ethylpyridin-3-yl)thiophen-2-yl)methanamine (DLCI-1), which inhibits the main enzyme that metabolizes nicotine, and we report a significant decrease in intravenous nicotine self-administration in male and female mice, supporting the potential of DLCI-1 as a novel tobacco cessation pharmacotherapeutic.

Published
2020

15. Egocentric social network structure, health, and pro-social behaviors in a national panel study of Americans.

Author

A James O'Malley, Samuel Arbesman, Darby Miller Steiger, James H Fowler, and Nicholas A Christakis

Subjects
Medicine, Science
Abstract

Using a population-based, panel survey, we study how egocentric social networks change over time, and the relationship between egocentric network properties and health and pro-social behaviors. We find that the number of prosocial activities is strongly positively associated with having more friends, or an increase in degree, with approximately 0.04 more prosocial behaviors expected for every friend added. Moreover, having more friends is associated with an improvement in health, while being healthy and prosocial is associated with closer relationships. Specifically, a unit increase in health is associated with an expected 0.45 percentage-point increase in average closeness, while adding a prosocial activity is associated with a 0.46 percentage-point increase in the closeness of one's relationships. Furthermore, a tradeoff between degree and closeness of social contacts was observed. As the number of close social contacts increases by one, the estimated average closeness of each individual contact decreases by approximately three percentage-points. The increased awareness of the importance of spillover effects in health and health care makes the ascertainment of egocentric social networks a valuable complement to investigations of the relationship between socioeconomic factors and health.

Published
2012
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16. Influence of Storm–Storm and Storm–Environment Interactions on Tropical Cyclone Formation and Evolution

Author

James P. Fowler and Thomas J. Galarneau

Subjects
Atmospheric Science, 010504 meteorology & atmospheric sciences, Meteorology, Climatology, Rossby wave, Environmental science, Storm, Tropical cyclone, 010502 geochemistry & geophysics, 01 natural sciences, 0105 earth and related environmental sciences
Abstract

The aim of this study is to examine the development of four tropical cyclones (TCs) in the North Atlantic basin in late August and early September 2010. This period is of interest because four consecutive easterly waves emerged from West Africa and resulted in a multiple TC event (MTCE) over the North Atlantic. The first two TCs—Danielle and Earl—quickly developed into TCs east of 40°W and eventually intensified into major hurricanes. Conversely, the last two TCs—Fiona and Gaston—developed more slowly reaching only weak tropical storm intensity at their peak. The close proximity and differing evolution of these four TCs provides a unique opportunity to examine how these TCs interacted with each other and their surrounding environment, which influenced their development as they moved westward across the North Atlantic. The results showed that concurrent extratropical cyclogenesis events over the western and eastern North Atlantic and the recurvature of TC Danielle produced increased meridional flow over the midlatitude North Atlantic. This increased meridional flow resulted in subsynoptic-scale regions of increased vertical wind shear in the subtropics, which delayed Earl’s development and led to Fiona’s demise. Additionally, increased meridional flow in midlatitudes contributed to anomalous drying of the subtropics. This dry air was entrained into Gaston’s circulation leading to reduced convection and weakening. These TC–TC and TC–environment interactions highlight the difficult challenge of forecasting TC genesis and position posed by MTCEs in a rapidly evolving synoptic-scale flow.

Published
2017

17. The spread of sleep loss influences drug use in adolescent social networks.

Author

Sara C Mednick, Nicholas A Christakis, and James H Fowler

Subjects
Medicine, Science
Abstract

Troubled sleep is a commonly cited consequence of adolescent drug use, but it has rarely been studied as a cause. Nor have there been any studies of the extent to which sleep behavior can spread in social networks from person to person to person. Here we map the social networks of 8,349 adolescents in order to study how sleep behavior spreads, how drug use behavior spreads, and how a friend's sleep behavior influences one's own drug use. We find clusters of poor sleep behavior and drug use that extend up to four degrees of separation (to one's friends' friends' friends' friends) in the social network. Prospective regression models show that being central in the network negatively influences future sleep outcomes, but not vice versa. Moreover, if a friend sleeps

Published
2010
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18. Nicotine Acts on Cholinergic Signaling Mechanisms to Directly Modulate Choroid Plexus Function

Author

Margaret Coutts, Edwin S. Monuki, Agenor Limon, William E. Bunney, Nickolas P. Grimes, Preston M. Cartagena, Valeria Lallai, Angelo Demuro, James P. Fowler, Christie D. Fowler, and P. Adolfo Sequeira

Subjects
Male, Nicotine, drug dependence, Endogeny, Receptors, Nicotinic, transthyretin, 03 medical and health sciences, 0302 clinical medicine, microRNA, medicine, Animals, Humans, Prealbumin, Nicotinic Agonists, Rats, Wistar, 030304 developmental biology, 0303 health sciences, choroid plexus, biology, Chemistry, General Neuroscience, 3.1, General Medicine, Middle Aged, New Research, Cell biology, Rats, Transthyretin, Nicotinic acetylcholine receptor, MicroRNAs, biology.protein, Cholinergic, Choroid plexus, Female, Disorders of the Nervous System, nicotinic acetylcholine receptors, sense organs, 030217 neurology & neurosurgery, Function (biology), medicine.drug, Signal Transduction, nicotine
Abstract

Neuronal cholinergic circuits have been implicated in cognitive function and neurological disease, but the role of cholinergic signaling in other cellular populations within the brain has not been as fully defined. Here, we show that cholinergic signaling mechanisms are involved in mediating the function of the choroid plexus, the brain structure responsible for generating CSF and releasing various factors into the brain. The choroid plexus was found to express markers of endogenous cholinergic signaling, including multiple nicotinic acetylcholine receptor (nAChR) subtypes in a region-specific manner, and application of nicotine was found to induce cellular activation, as evidenced by calcium influx in primary tissue. During intravenous nicotine self-administration in male rats, nicotine increased expression of transthyretin, a protein selectively produced and released by the choroid plexus, and microRNA-204 (mir-204), a transcript found in high levels in the choroid plexus and CSF. Finally, human choroid plexus tissue from both sexes was found to exhibit similar nAChR, transthyretin and mir-204 expression profiles, supporting the translational relevance of the findings. Together, these studies demonstrate functionally active cholinergic signaling mechanisms in the choroid plexus, the resulting effects on transthyretin and mir-204 expression, and reveal the direct mechanism by which nicotine modulates function of this tissue.

Published
2019

19. The Interpeduncular-Ventral Hippocampus Pathway Mediates Active Stress Coping and Natural Reward

Author

Malia Bautista, Christie D. Fowler, Edison Chen, Yasmine Sherafat, James P. Fowler, and Amina Ahmed

Subjects
Male, Agonist, Nicotine, anhedonia-associated behavior, Interpeduncular nucleus, Coping (psychology), hippocampus, medicine.drug_class, Interpeduncular Nucleus, stress coping behavior, Biology, Serotonergic, Basic Behavioral and Social Science, interpeduncular nucleus, Mice, Reward, Active stress, Adaptation, Psychological, Behavioral and Social Science, medicine, Animals, Adaptation, Receptor, General Neuroscience, Neurosciences, General Medicine, Brain Disorders, serotonin, Mental Health, Cognition and Behavior, Psychological, Serotonin, hippocannpus, Neuroscience, Research Article: New Research, medicine.drug
Abstract

Maladaptive stress-related behaviors are integral to multiple complex psychiatric disorders, and it has been well established that serotonergic signaling mediates various aspects of these maladaptive states. In these studies, we sought to uncover the function of a previously undefined serotonergic pathway, which projects from the interpeduncular nucleus (IPN) to the ventral hippocampus (vHipp). Intersectional retrograde and chemogenetic viral manipulation strategies were employed to manipulate the function of the IPN-vHipp pathway during a variety of behavioral measures in male mice. We found a significant effect of circuit inhibition on behaviors associated with coping strategies and natural reward. Specifically, inhibition of the IPN-vHipp pathway dramatically increased active stress-induced escape behaviors, in addition to moderately affecting sucrose consumption and food self-administration. During inhibition of this pathway, agonist activation of serotonergic 5-HT2A/2Creceptors in the vHipp reversed the effects of IPN-vHipp circuit inhibition on active escape behaviors, thereby supporting the synaptic mechanism underlying the behavioral effects evidenced. IPN-vHipp inhibition did not induce differences in generalized locomotion, anxiety-associated behavior, and intravenous nicotine self-administration. Importantly, these findings are in opposition to the canonical understanding of serotonin in such escape behaviors, indicating that serotonin exerts opposing effects on behavior in a pathway-specific manner in the brain. Taken together, these findings thereby have important implications for our understanding of serotonergic signaling and associated therapeutic approaches for the treatment of disease symptomology.

Published
2020

20. Altered Baseline and Nicotine-Mediated Behavioral and Cholinergic Profiles in ChAT-Cre Mouse Lines

Author

James P. Fowler, Yasmine Sherafat, Valeria Lallai, Anna N. Pushkin, Edison Chen, Christie D. Fowler, and Nickolas P. Grimes

Subjects
0301 basic medicine, Male, Chromosomes, Artificial, Bacterial, Vesicular Acetylcholine Transport Proteins, Hippocampus, Medical and Health Sciences, Transgenic, Nicotine, Mice, 0302 clinical medicine, Models, Nicotinic Agonists, Research Articles, Behavior, Animal, General Neuroscience, Bacterial, Choline acetyltransferase, Mental Health, Genetic Techniques, Artificial, Models, Animal, Female, Locomotion, medicine.drug, Genetically modified mouse, mice, Transgene, education, Cre recombinase, Mice, Transgenic, Biology, Internal Ribosome Entry Sites, Basic Behavioral and Social Science, Chromosomes, Choline O-Acetyltransferase, 03 medical and health sciences, intravenous nicotine self-administration, Vesicular acetylcholine transporter, Behavioral and Social Science, medicine, Genetics, Animals, cre recombinase, Behavior, Neurology & Neurosurgery, Integrases, Animal, Psychology and Cognitive Sciences, Neurosciences, choline acetyltransferase, acetylcholine, 030104 developmental biology, Cholinergic, Neuroscience, 030217 neurology & neurosurgery
Abstract

The recent development of transgenic rodent lines expressing cre recombinase in a cell-specific manner, along with advances in engineered viral vectors, has permitted in-depth investigations into circuit function. However, emerging evidence has begun to suggest that genetic modifications may introduce unexpected caveats. In the current studies, we sought to extensively characterize male and female mice from both the ChAT(BAC)-Cre mouse line, created with the bacterial artificial chromosome (BAC) method, and ChAT(IRES)-Cre mouse line, generated with the internal ribosome entry site (IRES) method. ChAT(BAC)-Cre transgenic and wild-type mice did not differ in general locomotor behavior, anxiety measures, drug-induced cataplexy, nicotine-mediated hypolocomotion, or operant food training. However, ChAT(BAC)-Cre transgenic mice did exhibit significant deficits in intravenous nicotine self-administration, which paralleled an increase in vesicular acetylcholine transporter and choline acetyltransferase (ChAT) hippocampal expression. For the ChAT(IRES)-Cre line, transgenic mice exhibited deficits in baseline locomotor, nicotine-mediated hypolocomotion, and operant food training compared with wild-type and hemizygous littermates. No differences among ChAT(IRES)-Cre wild-type, hemizygous, and transgenic littermates were found in anxiety measures, drug-induced cataplexy, and nicotine self-administration. Given that increased cre expression was present in the ChAT(IRES)-Cre transgenic mice, as well as a decrease in ChAT expression in the hippocampus, altered neuronal function may underlie behavioral phenotypes. In contrast, ChAT(IRES)-Cre hemizygous mice were more similar to wild-type mice in both protein expression and the majority of behavioral assessments. As such, interpretation of data derived from ChAT-Cre rodents must consider potential limitations dependent on the line and/or genotype used in research investigations.SIGNIFICANCE STATEMENTAltered baseline and/or nicotine-mediated behavioral profiles were discovered in transgenic mice from the ChAT(BAC)-Cre and ChAT(IRES)-Cre lines. Given that these cre-expressing mice have become increasingly used by the scientific community, either independently with chemicogenetic and optogenetic viral vectors or crossed with other transgenic lines, the current studies highlight important considerations for the interpretation of data from previous and future experimental investigations. Moreover, the current findings detail the behavioral effects of either increased or decreased baseline cholinergic signaling mechanisms on locomotor, anxiety, learning/memory, and intravenous nicotine self-administration behaviors.

Published
2017

21. Cannabinoid and nicotine exposure during adolescence induces sex-specific effects on anxiety- and reward-related behaviors during adulthood

Author

Alan Torres-Mendoza, Angeline J. Eugene, James P. Fowler, Valeria Lallai, Anna N. Pushkin, Edison Chen, Christie D. Fowler, and Homberg, Judith

Subjects
Male, Sucrose, Physiology, medicine.medical_treatment, Social Sciences, Anxiety, Disaccharides, Dissociative, Nicotine, Mice, 0302 clinical medicine, Medicine and Health Sciences, Psychology, Medicine, Pediatric, Mammals, Sex Characteristics, Multidisciplinary, Animal Behavior, biology, Organic Compounds, Substance Abuse, Cognitive flexibility, Eukaryota, Drugs, humanities, Chemistry, Physiological Parameters, Behavioral Pharmacology, Vertebrates, Physical Sciences, Mental health, Female, medicine.symptom, Locomotion, psychological phenomena and processes, Research Article, Sex characteristics, medicine.drug, Agonist, Pediatric Research Initiative, Drug Abuse (NIDA Only), medicine.medical_specialty, General Science & Technology, medicine.drug_class, Morpholines, Science, Carbohydrates, Naphthalenes, Basic Behavioral and Social Science, Rodents, Operant, 03 medical and health sciences, Reward, Recreational Drug Use, Internal medicine, Tobacco, Behavioral and Social Science, MD Multidisciplinary, Animals, Humans, Cannabis, Pharmacology, Behavior, Tobacco Smoke and Health, Cannabinoid Research, Cannabinoids, Biological Locomotion, Animal, business.industry, Body Weight, Organic Chemistry, Organisms, Chemical Compounds, Biology and Life Sciences, biology.organism_classification, Benzoxazines, 030227 psychiatry, Disease Models, Animal, Endocrinology, Amniotes, Disease Models, Conditioning, Operant, Cannabinoid, business, Zoology, 030217 neurology & neurosurgery, Conditioning
Abstract

Nicotine and cannabis use during adolescence has the potential to induce long lasting changes on affective and cognitive function. Here, we examined whether adolescent exposure to nicotine, the cannabinoid agonist WIN55-212,2 (WIN), or co-exposure to both would alter operant learning, locomotion, and anxiety- and reward-related behaviors in male and female mice during adulthood. Males exposed to a moderate dose of WIN (2 mg/kg) or co-exposed to nicotine and the moderate dose of WIN exhibited decreased anxiety-associated behaviors and increased cognitive flexibility, but did not differ in operant learning or generalized locomotion. In contrast, differences were not found among the females in these measures at the moderate WIN dose or in both sexes with exposure to a low WIN dose (0.2 mg/kg). Furthermore, a sex-dependent dissociative effect was found in natural reward consumption. Males exposed to the moderate dose of WIN or co-exposed to nicotine and the moderate dose of WIN demonstrated increased sucrose consumption. In contrast, females exposed to the moderate dose of WIN exhibited a decrease in sucrose consumption, which was ameliorated with co-administration of nicotine. Together, these novel findings demonstrate that adolescent exposure to cannabinoids in the presence or absence of nicotine results in altered affective and reward-related behaviors during adulthood.

Published
2019

22. Carex nigra

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1380306%5DMICH-V-1380306, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1380306/MICH-V-1380306/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Published
1900

23. Carex hormathodes

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1373316%5DMICH-V-1373316, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1373316/MICH-V-1373316/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Published
1901

24. Carex canescens

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1365136%5DMICH-V-1365136, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1365136/MICH-V-1365136/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Published
1900

25. Agrostis gigantea

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1403543%5DMICH-V-1403543, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1403543/MICH-V-1403543/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Published
1907

26. Carex umbellata

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1390804%5DMICH-V-1390804, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1390804/MICH-V-1390804/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Published
1906

27. Carex tenera

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1389229%5DMICH-V-1389229, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1389229/MICH-V-1389229/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Published
1885

28. Carex retrorsa

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1384907%5DMICH-V-1384907, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1384907/MICH-V-1384907/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Published
1902

29. Carex communis var. communis

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1366139%5DMICH-V-1366139, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1366139/MICH-V-1366139/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

Published
1906

30. Eriophorum callitrix

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1395415%5DMICH-V-1395415, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1395415/MICH-V-1395415/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

31. Stellaria borealis subsp. borealis

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1565256%5DMICH-V-1565256, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1565256/MICH-V-1565256/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

32. Stellaria alsine

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1565257%5DMICH-V-1565257, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1565257/MICH-V-1565257/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

33. Stellaria alsine

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1565251%5DMICH-V-1565251, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1565251/MICH-V-1565251/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

34. Carex debilis var. rudgei

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1564296%5DMICH-V-1564296, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1564296/MICH-V-1564296/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

35. Carex paleacea

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1382000%5DMICH-V-1382000, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1382000/MICH-V-1382000/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

36. Carex nigra

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1380331%5DMICH-V-1380331, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1380331/MICH-V-1380331/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

37. Carex lenticularis var. lenticularis

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1376021%5DMICH-V-1376021, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1376021/MICH-V-1376021/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

38. Salix bebbiana

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1453115%5DMICH-V-1453115, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1453115/MICH-V-1453115/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

39. Salix bebbiana

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1453116%5DMICH-V-1453116, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1453116/MICH-V-1453116/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

40. Juncus pylaei

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1449254%5DMICH-V-1449254, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1449254/MICH-V-1449254/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

41. Juncus balticus

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1446857%5DMICH-V-1446857, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1446857/MICH-V-1446857/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

42. Solidago bicolor

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1442951%5DMICH-V-1442951, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1442951/MICH-V-1442951/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

43. Euthamia graminifolia

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1442609%5DMICH-V-1442609, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1442609/MICH-V-1442609/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

44. Potamogeton perfoliatus

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1441200%5DMICH-V-1441200, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1441200/MICH-V-1441200/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

45. Persicaria sagittata

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1439498%5DMICH-V-1439498, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1439498/MICH-V-1439498/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

46. Persicaria maculosa

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1439173%5DMICH-V-1439173, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1439173/MICH-V-1439173/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

47. Persicaria hydropiper

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1438827%5DMICH-V-1438827, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1438827/MICH-V-1438827/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

48. Alnus viridis subsp. crispa

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1436170%5DMICH-V-1436170, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1436170/MICH-V-1436170/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

49. Alnus viridis subsp. crispa

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1436139%5DMICH-V-1436139, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1436139/MICH-V-1436139/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

50. Alnus incana subsp. rugosa

Author

James P. Fowler, James P. Fowler, James P. Fowler, and James P. Fowler

Abstract

Angiosperms, http://name.umdl.umich.edu/IC-HERB00IC-X-1435894%5DMICH-V-1435894, https://quod.lib.umich.edu/cgi/i/image/api/thumb/herb00ic/1435894/MICH-V-1435894/!250,250, The University of Michigan Library provides access to these materials for educational and research purposes. Some materials may be protected by copyright. If you decide to use any of these materials, you are responsible for making your own legal assessment and securing any necessary permission. If you have questions about the collection, please contact the Herbarium professional staff: herb-dlps-help@umich.edu. If you have concerns about the inclusion of an item in this collection, please contact Library Information Technology: libraryit-info@umich.edu., https://www.lib.umich.edu/about-us/policies/copyright-policy

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