Life Sciences Commons^™

Fecal Microbiota Transplant Rescues Mice From Sepsis Due To Multi-Drug Resistant Healthcare Pathogens By Restoring Systemic Immunity, Sangman Michael Kim, Jennifer R. Defazio, Sanjiv K. Hyoju, Kishan Sangani, Robert Keskey, Monika A. Krezalek, Nikolai N. Khodarev, Naseer Sangwan, Scott Christley, Katharine G. Harris, Ankit Malik, Alexander Zaborin, Romain Bouziat, Diana R. Ranoa, Mara Wiegerinck, Jordan D. Ernest, Baddr A. Shakhsheer, Irma D. Fleming, Ralph R. Weichselbaum, Dionysios A. Antonopoulos, Jack A. Gilbert, Luis B. Barreiro, Olga Zaborina, Bana Jabri, John C. Alverdy

Biology Faculty Publications

Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity …

Mice Fed An Obesogenic Western Diet, Administered Antibiotics, And Subjected To A Sterile Surgical Procedure Develop Lethal Septicemia With Multidrug-Resistant Pathobionts, Sanjiv K. Hyoju, Alexander Zaborin, Robert Keskey, Anukriti Sharma, Wyatt Arnold, Fons Van Den Berg, Sangman Michael Kim, Neil Gottel, Cindy Bethel, Angella Charnot-Katsikas, Peng Jianxin, Carleen Adriaansens, Emily Papazian, Jack A. Gilbert, Olga Zaborina, John C. Alverdy

Biology Faculty Publications

Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the …

Effect Of Human Cytomegalovirus (Hcmv) Us27 On Cxcr4 Receptor Internalization Measured By Fluorogen-Activating Protein (Fap) Biosensors, J. M. Boeck, Juliet Spencer

Biology Faculty Publications

Human cytomegalovirus (HCMV) is a widespread pathogen and a member of the Herpesviridae family. HCMV has a large genome that encodes many genes that are non-essential for virus replication but instead play roles in manipulation of the host immune environment. One of these is the US27 gene, which encodes a protein with homology to the chemokine receptor family of G protein-coupled receptors (GPCRs). The US27 protein has no known chemokine ligands but can modulate the signaling activity of host receptor CXCR4. We investigated the mechanism for enhanced CXCR4 signaling in the presence of US27 using a novel biosensor system comprised …

Human Cytomegalovirus Interleukin-10 Enhances Matrigel Invasion Of Mda-Mb-231 Breast Cancer Cells, Cendy Valle Oseguera, Juliet Spencer

Biology Faculty Publications

Background: While some risk factors for breast cancer are well-known, the influence of other factors, particularly virus infection, remains unclear. Human cytomegalovirus (HCMV) is widespread in the general population, and both molecular and epidemiological evidence has indicated links between HCMV and breast cancer. The HCMV protein cmvIL-10 is a potent suppressor of immune function that has also been shown to promote proliferation and migration of breast cancer cells. In this study, the impact of cmvIL-10 on tumor cell invasion through a simulated basement membrane was investigated.

Results: MDA-MB-231 breast cancer cells exhibited invasion through a matrigel layer that was significantly …

Role-Playing In A Vaccination Debate Strengthens Student Scientific Debate Skills For Various Audiences, Gianne Souza, P. F. Mixter

Biology Faculty Publications

Students are surrounded by strongly-held viewpoints on scientific topics and frequently discuss news reports with their classmates. We developed the vaccination debate exercise to leverage this interest and develop core higher-order cognitive skills (HOCS), including, but not limited to, the ability to critique public media or primary research sources and create arguments for defending multiple viewpoints. Students prepared to debate different sides of the topic and then randomly assumed one of the roles: “Physician” (pro-vaccine), “Activist” (anti-vaccination), or “Parent-on-the-fence” (undecided). Students reported an increase in their abilities to discuss scientific topics with diverse audiences and an increased awareness of importance …

Ten Simple Rules For Digital Data Storage, E. M. Hart, P. Barmby, D. Lebauer, F. Michonneau, S. Mount, P. Mulrooney, T. Poisot, K. H. Woo, Naupaka B. Zimmerman, J. W. Hollister

Biology Faculty Publications

No abstract provided.

Altitudinal Shifts Of The Native And Introduced Flora Of California In The Context Of 20th-Century Warming, A. Wolf, Naupaka B. Zimmerman, W. R. Anderegg, P. E. Busby, J. Christensen

Biology Faculty Publications

Aim: The differential responses of plant species to climate change are of great interest and grave concern for scientists and conservationists. One underexploited resource for better understanding these changes are the records held by herbaria. Using these records to assess the responses of different groups of species across the entire flora of California, we sought to quantify the magnitude of species elevational shifts, to measure differences in shifts among functional groups and between native and introduced species, and to evaluate whether these shifts were related to the conservation of thermal niches.

Location: California.

Methods: To characterize these shifts in California, …

Behavioral And Neural Indices Of Metacognitive Sensitivity In Preverbal Infants, Louise Goupil, Sid Kouider

Biology Faculty Publications

Humans adapt their behavior not only by observing the consequences of their actions but also by internally monitoring their performance. This capacity, termed metacognitive sensitivity [1 ; 2], has traditionally been denied to young children because they have poor capacities in verbally reporting their own mental states [3; 4 ; 5]. Yet, these observations might reflect children’s limited capacities for explicit self-reports, rather than limitations in metacognition per se. Indeed, metacognitive sensitivity has been shown to reflect simple computational mechanisms [1; 6; 7 ; 8], and can be found in various …

Neural And Neuroendocrine Processing Of A Non-Photic Cue In An Opportunistically Breeding Songbird, Darcy K. Ernst, G. E. Bentley

Biology Faculty Publications

Recent studies of the onset of breeding in long-day photoperiodic breeders have focused on the roles of type 2 and 3 iodothyronine deiodinases (DIO2 and DIO3) in the conversion of thyroxine (T4) to triiodothyronine (T3) and subsequent activation of the reproductive axis. It has been hypothesized that an increase in DIO2 and a reciprocal decrease in DIO3 causes the release of gonadotropinreleasing hormone (GnRH) from the hypothalamus, setting off a reproductive cascade, and that this DIO mechanism for GnRH release is conserved across vertebrate taxa. We sought to test whether social cues that are known to stimulate reproductive behaviors can …

The High Cost Of Reproduction In Sea Otters Necessitates Unique Physiological Adaptations, Nicole Thometz, T. L. Kendall, B. P. Richter, T. M. Williams

Biology Faculty Publications

Resting Superimposed on inherently high basal metabolic demands, the additional energetic requirements of reproduction can push female sea otters beyond physiological limits. Indeed, the resulting energy imbalance contributes to disproportionately high rates of mortality at the end of lactation in this species. To examine and quantify metabolic changes associated with reproduction, we measured the resting metabolic rate (RMR) of a female sea otter across gestation, lactation and non-reproductive periods. Concurrently, measurements were made on a non-breeding control female. Our results suggest that RMR declines during gestation. Conversely, RMR increases during lactation, reaches a peak at 3–4 months postpartum, and remains …

Comparative And Cumulative Energetic Costs Of Odontocete Responses To Anthropogenic Disturbance, Dawn P. Noren, Marla M. Holt, Robin C. Dunkin, Nicole Thometz, Terrie M. Williams

Biology Faculty Publications

Odontocetes respond to vessels and anthropogenic noise by modifying vocal behavior, surface active behaviors, dive patterns, swim speed, direction of travel, and activity budgets. Exposure scenarios and behavioral responses vary across odontocetes. A literature review was conducted to determine relevant sources of disturbance and associated behavioral responses for several odontocete species (bottlenose dolphin, killer whale, harbor porpoise, and beaked whales). The energetic costs of species-specific responses to anthropogenic disturbance were then estimated. The energetic impact varies across species and scenarios as well as by behavioral responses. Overall, the cumulative energetic cost of ephemeral behavioral responses (e.g., performing surface active behaviors, …

Limited Role Of Functional Differentiation In Early Diversification Of Animals, Matthew L. Knope, N A. Heim, L O. Frishkoff, J L. Payne

Biology Faculty Publications

The origin of most animal phyla and classes during the Cambrian explosion has been hypothesized to represent an ‘early burst’ of evolutionary exploration of functional ecological possibilities. However, the ecological history of marine animals has yet to be fully quantified, preventing an assessment of the early-burst model for functional ecology. Here we use ecological assignments for 18,621 marine animal genera to assess the relative timing of functional differentiation versus taxonomic diversification from the Cambrian to the present day. We find that functional diversity increased more slowly than would be expected given the history of taxonomic diversity. Contrary to previous inferences …

The Tao Of Open Science For Ecology, S. E. Hampton, S. S. Anderson, S. C. Bagby, C. Gries, X. Han, E. M. Hart, M. B. Jones, W. C. Lenhardt, A. Macdonald, W. K. Michener, J. Mudge, A. Pourmokhtarian, M. P. Schildhauer, K. H. Woo, Naupaka B. Zimmerman

Biology Faculty Publications

The field of ecology is poised to take advantage of emerging technologies that facilitate the gathering, analyzing, and sharing of data, methods, and results. The concept of transparency at all stages of the research process, coupled with free and open access to data, code, and papers, constitutes “open science.” Despite the many benefits of an open approach to science, a number of barriers to entry exist that may prevent researchers from embracing openness in their own work. Here we describe several key shifts in mindset that underpin the transition to more open science. These shifts in mindset include thinking about …

Altered Gene Expression In The Schistosome-Transmitting Snail Biomphalaria Glabrata Following Exposure To Niclosamide, The Active Ingredient In The Widely Used Molluscicide Bayluscide, Si-Ming Zhang, S K. Buddenborg, C M. Adema, John T. Sullivan, E S. Loker

Biology Faculty Publications

In view of the call by the World Health Organization (WHO) for elimination of schistosomiasis as a public health problem by 2025, use of molluscicides in snail control to supplement chemotherapy–based control efforts is likely to increase in the coming years. The mechanisms of action of niclosamide, the active ingredient in the most widely used molluscicides, remain largely unknown. A better understanding of its toxicology at the molecular level will both improve our knowledge of snail biology and may offer valuable insights into the development of better chemical control methods for snails. We used a recently developed Biomphalaria glabrata oligonucleotide …

An Integrative Approach To Phylogeography: Investigating The Effects Of Ancient Seaways, Climate, And Historical Geology On Multi-Locus Phylogeographic Boundaries Of The Arboreal Salamander (Aneides Lugubris), S B. Reilly, Ammon Corl, D B. Wake

Biology Faculty Publications

Background: Phylogeography is an important tool that can be used to reveal cryptic biodiversity and to better understand the processes that promote lineage diversification. We studied the phylogeographic history of the Arboreal Salamander (Aneides lugubris), a wide-ranging species endemic to the California floristic province. We used multi-locus data to reconstruct the evolutionary history of A. lugubris and to discover the geographic location of major genetic breaks within the species. We also used species distribution modeling and comparative phylogeography to better understand the environmental factors that have shaped the genetic history of A. lugubris.

Results: We found six major mitochondrial clades …

The Next Generation Of Action Ecology: Novel Approaches Towards Global Ecological Research, R. L. White, A. E. Sutton, R. Salguero-Gómez, T. C. Bray, H. Campbell, E. Cieraad, N. Geekiyanage, L. Gherardi, A. C. Hughes, P. Søgaard Jørgensen, T. Poisot, Lucía Desoto, Naupaka B. Zimmerman

Biology Faculty Publications

Advances in the acquisition and dissemination of knowledge over the last decade have dramatically reshaped the way that ecological research is conducted. The advent of large, technology-based resources such as iNaturalist, Genbank, or the Global Biodiversity Information Facility (GBIF) allow ecologists to work at spatio-temporal scales previously unimaginable. This has generated a new approach in ecological research: one that relies on large datasets and rapid synthesis for theory testing and development, and findings that provide specific recommendations to policymakers and managers. This new approach has been termed action ecology, and here we aim to expand on earlier definitions to …

Ecology Postdocs In Academia: Primary Concerns And Possible Solutions, A. K. Shaw, D. E. Stanton, S. R. Supp, A. Budden, S. Eby, P. L. Reynolds, R. Salguero-Gómez, D. R. Scholes, Naupaka B. Zimmerman

Biology Faculty Publications

No abstract provided.

Connecting People And Ideas From Around The World: Global Innovation Platforms For Next-Generation Ecology And Beyond, P. Søgaard Jørgensen, F. Barraquand, V. Bonhomme, T. J. Curran, E. Cieraad, T. G. Ezard, L. Gherardi, R. A. Hayes, T. Poisot, R. Salguero-Gómez, Lucía Desoto, B. Swartz, J. M. Talbot, B. Wee, Naupaka B. Zimmerman

Biology Faculty Publications

We present a case for using Global Community Innovation Platforms (GCIPs), an approach to improve innovation and knowledge exchange in international scientific communities through a common and open online infrastructure. We highlight the value of GCIPs by focusing on recent efforts targeting the ecological sciences, where GCIPs are of high relevance given the urgent need for interdisciplinary, geographical, and cross-sector collaboration to cope with growing challenges to the environment as well as the scientific community itself. Amidst the emergence of new international institutions, organizations, and meetings, GCIPs provide a stable international infrastructure for rapid and long-term coordination that can be …

Human Cytomegalovirus Interleukin-10 Promotes Proliferation And Migration Of Mcf-7 Breast Cancer Cells, Robin K. Bishop, Cendy A. Valle Oseguera, Juliet Spencer

Biology Faculty Publications

Breast cancer is the most common malignancy affecting women worldwide. While a small fraction of breast cancers have a hereditary component, environmental and behavioral factors also impact the development of cancer. Human cytomegalovirus (HCMV) is a member of the Herpesviridae family that is widespread in the general population and has been linked to several forms of cancer. While HCMV DNA has been found in some breast cancer tissue specimens, we wanted to investigate whether a secreted viral cytokine might have an effect on cancerous or even pre-cancerous cells. HCMV encodes an ortholog of the human cellular cytokine interleukin-10 (IL-10). The …

Exercise At Depth Alters Bradycardia And Incidence Of Cardiac Anomalies In Deep-Diving Marine Mammals, T. M. Williams, L. A. Fuiman, T. Kendall, P. Berry, B. Richter, S. R. Noren, Nicole Thometz, M. J. Shattock, E. Farrell, A. M. Stamper, R. W. Davis

Biology Faculty Publications

Unlike their terrestrial ancestors, marine mammals routinely confront extreme physiological and physical challenges while breath-holding and pursuing prey at depth. To determine how cetaceans and pinnipeds accomplish deep-sea chases, we deployed animal-borne instruments that recorded high-resolution electrocardiograms, behaviour and flipper accelerations of bottlenose dolphins (Tursiops truncatus) and Weddell seals (Leptonychotes weddellii) diving from the surface to 4200 m. Here we report that both exercise and depth alter the bradycardia associated with the dive response, with the greatest impacts at depths inducing lung collapse. Unexpectedly, cardiac arrhythmias occurred in 473% of deep, aerobic dives, which we attribute to the interplay between …

Energetic Demands Of Immature Sea Otters From Birth To Weaning: Implications For Maternal Costs, Reproductive Behavior And Population-Level Trends, Nicole Thometz, M. T. Tinker, M. M. Staedler, K. A. Mayer, T. M. Williams

Biology Faculty Publications

Sea otters (Enhydra lutris) have the highest mass-specific metabolic rate of any marine mammal, which is superimposed on the inherently high costs of reproduction and lactation in adult females. These combined energetic demands have been implicated in the poor body condition and increased mortality of female sea otters nearing the end of lactation along the central California coast. However, the cost of lactation is unknown and currently cannot be directly measured for this marine species in the wild. Here, we quantified the energetic demands of immature sea otters across five developmental stages as a means of assessing the …

Inducing Task-Relevant Responses To Speech In The Sleeping Brain, Sid Kouider, Thomas Andrillon, Leonardo S. Barbosa, Louise Goupil, Tristan A. Bekinschtein

Biology Faculty Publications

Falling asleep leads to a loss of sensory awareness and to the inability to interact with the environment [1]. While this was traditionally thought as a consequence of the brain shutting down to external inputs, it is now acknowledged that incoming stimuli can still be processed, at least to some extent, during sleep [2]. For instance, sleeping participants can create novel sensory associations between tones and odors [3] or reactivate existing semantic associations, as evidenced by event-related potentials [4; 5; 6 ; 7]. Yet, the extent to which the brain …

The Dry Box And C-Terminal Domain Of The Human Cytomegalovirus Us27 Gene Product Play A Role In Promoting Cell Growth And Survival, C C. Tu, Juliet Spencer

Biology Faculty Publications

Human cytomegalovirus (HCMV) is a widespread pathogen that can lay dormant in healthy individuals and establish lifelong latent infection. This successful co-existence is facilitated by a number of viral gene products that manipulate host cellular functions and immune responses. Among these immunomodulatory genes are four G-protein coupled receptors (GPCRs) encoded by HCMV, designated US27, US28, UL33, and UL78. Studies have shown the US28 gene product to be a functional chemokine receptor that signals both constitutively and in a ligand-dependent manner, resulting in a wide range of cellular effects. In previous work, we have found that US27 expression results in at …

Cmvil-10 Stimulates The Invasive Potential Of Mda-Mb-231 Breast Cancer Cells, Cendy Valle Oseguera, Juliet Spencer

Biology Faculty Publications

Cancer is the result of unregulated cell growth that leads to tumor formation, and in many cases, metastases. Although there are several risk factors associated with cancer, one area that remains poorly understood is the impact of infectious disease. Human cytomegalovirus (HCMV) is a member of the herpesvirus family that is highly prevalent in the population. HCMV usually causes clinical disease only in immune compromised individuals, but recent evidence suggests that HCMV may be strongly associated with some forms of cancer, particularly glioblastoma and breast cancer. We investigated the possibility that cmvIL-10, a viral cytokine with homology to human IL-10 …

Lack Of Quantitative Training Among Early-Career Ecologists: A Survey Of The Problem And Potential Solutions, F. Barraquand, T. G. Ezard, P. Søgaard Jørgensen, Naupaka B. Zimmerman, S. Chamberlain, R. Salguero-Gómez, T. J. Curran, T. Poisot

Biology Faculty Publications

Proficiency in mathematics and statistics is essential to modern ecological science, yet few studies have assessed the level of quantitative training received by ecologists. To do so, we conducted an online survey. The 937 respondents were mostly early-career scientists who studied biology as undergraduates. We found a clear self-perceived lack of quantitative training: 75% were not satisfied with their understanding of mathematical models; 75% felt that the level of mathematics was “too low” in their ecology classes; 90% wanted more mathematics classes for ecologists; and 95% more statistics classes. Respondents thought that 30% of classes in ecology-related degrees should be …

The Unseen World: Environmental Microbial Sequencing And Identification Methods For Ecologists, Naupaka B. Zimmerman, J. Izard, C. Klatt, J. Zhou, E. Aronson

Biology Faculty Publications

Microorganisms inhabit almost every environment, comprise the majority of diversity on Earth, are important in biogeochemical cycling, and may be vital to ecosystem responses to large-scale climatic change. In recent years, ecologists have begun to use rapidly advancing molecular techniques to address questions about microbial diversity, biogeography, and responses to environmental change. Studies of microbes in the environment generally focus on three broad objectives: determining which organisms are present, what their functional capabilities are, and which are active at any given time. However, comprehending the range of methodologies currently in use can be daunting. To provide an overview of environmental …

Direct Fitness Correlates And Thermal Consequences Of Facultative Aggregation In A Desert Lizard, Alison R. Davis Rabosky, Ammon Corl, Heather E.M. Liwanag, Yann Surget-Groba, Barry Sinervo

Biology Faculty Publications

Social aggregation is a common behavioral phenomenon thought to evolve through adaptive benefits to group living. Comparing fitness differences between aggregated and solitary individuals in nature – necessary to infer an evolutionary benefit to living in groups – has proven difficult because communally-living species tend to be obligately social and behaviorally complex. However, these differences and the mechanisms driving them are critical to understanding how solitary individuals transition to group living, as well as how and why nascent social systems change over time. Here we demonstrate that facultative aggregation in a reptile (the Desert Night Lizard, Xantusia vigilis) confers …

Receptor Chimeras Demonstrate That The C-Terminal Domain Of The Human Cytomegalovirus Us27 Gene Product Is Necessary And Sufficient For Intracellular Receptor Localization, Lance K. Stapleton, Kathleen L. Arnolds, Angela P. Lares, Tori M. Devito, Juliet V. Spencer

Biology Faculty Publications

Background

Human cytomegalovirus (HCMV) is ubiquitous in the population but generally causes only mild or asymptomatic infection except in immune suppressed individuals. HCMV employs numerous strategies for manipulating infected cells, including mimicry of G-protein coupled receptors (GPCRs). The HCMV US27 gene product is a putative GPCR, yet no ligand or signaling has been identified for this receptor. In the present study, immunofluorescence microscopy was used to examine the cellular distribution of wild type US27, as well as US27 deletion mutants and chimeric receptors.

Results

In transiently transfected cells, wild type US27 was found primarily in intracellular compartments, in striking contrast …

Quantifying The Impact Of Gene Flow On Phenotype-Environment Mismatch: A Demonstration With The Scarlet Monkeyflower Mimulus Cardinalis, John R. Paul, Seema N. Sheth, Amy L. Angert

Biology Faculty Publications

Geographic range margins offer testing grounds for limits to adaptation. If range limits are concordant with niche limits, range expansions require the evolution of new phenotypes that can maintain populations beyond current range margins. However, many species' range margins appear static over time, suggesting limits on the ability of marginal populations to evolve appropriate phenotypes. A potential explanation is the swamping gene flow hypothesis, which posits that asymmetrical gene flow from large, well-adapted central populations prevents marginal populations from locally adapting. We present an empirical framework for combining gene flow, environment, and fitness-related phenotypes to infer the potential for maladaptation, …

Functional Characterization Of Putative Cilia Genes By High-Content Analysis, Cary Lai, Nidhi Gupta, Xiaohui Wen, Linda Rangell, Ben Chih, Andrew S. Peterson, J Fernando Bazan, Li Li, Suzie J. Scales

Biology Faculty Publications

Cilia are microtubule-based protrusions from the cell surface that are involved in a number of essential signaling pathways, yet little is known about many of the proteins that regulate their structure and function. A number of putative cilia genes have been identified by proteomics and comparative sequence analyses, but functional data are lacking for the vast majority. We therefore monitored the effects in three cell lines of small interfering RNA (siRNA) knockdown of 40 of these genes by high-content analysis. We assayed cilia number, length, and transport of two different cargoes (membranous serotonin receptor 6-green fluorescent protein [HTR6-GFP] and the …