Biology Commons^™

Metals And Metal Complexes In Diseases With A Focus On Covid-19: Facts And Opinions, Agnieszka Ścibior, Manuel Aureliano, Alvin A. Holder, Juan Llopis

Chemistry & Biochemistry Faculty Publications

In the present Special Issue on “Metals and Metal Complexes in Diseases with a Focus on COVID-19: Facts and Opinions”, an attempt has been made to include reports updating our knowledge of elements considered to be potential candidates for therapeutic applications and certain metal-containing species, which are extensively being examined towards their potential biomedical use due to their specific physicochemical properties. The Special Issue compiles data on the role of metals in COVID-19 and focuses on other illnesses and biological processes that affect metal metabolism. It consists of eight manuscripts, including five review articles and three original research papers (Figure …

Newer Surveillance Data Extends Our Understanding Of The Niche Of Rickettsia Montanensis (Rickettsiales: Rickettsiaceae) Infection Of The American Dog Tick (Acari: Ixodidae) In The United States, Catherine A. Lippi, Holly D. Gaff, Robyn M. Nadolny, Sadie J. Ryan

Biological Sciences Faculty Publications

Background: Understanding the geographic distribution of Rickettsia montanensis infections in Dermacentor variabilis is important for tick-borne disease management in the United States, as both a tick-borne agent of interest and a potential confounder in surveillance of other rickettsial diseases. Two previous studies modeled niche suitability for D. variabilis with and without R. montanensis, from 2002-2012, indicating that the D. variabilis niche overestimates the infected niche. This study updates these, adding data since 2012.

Methods: Newer surveillance and testing data were used to update Species Distribution Models (SDMs) of D. variabilis, and R. montanensis infected D. variabilis, in …

Rickettsial Pathogen Perturbs Tick Circadian Gene To Infect The Vertebrate Host, Supreet Khanal, Vikas Taank, John F. Anderson, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ixodes scapularis is a medically important tick that transmits several microbes to humans, including rickettsial pathogen Anaplasma phagocytophilum. In nature, these ticks encounter several abiotic factors including changes in temperature, humidity, and light. Many organisms use endogenously generated circadian pathways to encounter abiotic factors. In this study, we provide evidence for the first time to show that A. phagocytophilum modulates the arthropod circadian gene for its transmission to the vertebrate host. We noted a circadian oscillation in the expression of arthropod clock, bmal1, period and timeless genes when ticks or tick cells were exposed to alternate 12 h …

Tick Ecdysteroid Hormone, Global Microbiota/Rickettsia Signaling In The Ovary Versus Carcass During Vitellogenesis In Part-Fed (Virgin) American Dog Ticks, Dermacentor Variabilis, Loganathan Ponnusamy, Haley Sutton, Robert D. Mitchell Iii, Daniel E. Sonenshine, Charles S. Apperson, Richard Michael Roe

Biological Sciences Faculty Publications

The transovarial transmission of tick-borne bacterial pathogens is an important mechanism for their maintenance in natural populations and transmission, causing disease in humans and animals. The mechanism for this transmission and the possible role of tick hormones facilitating this process have never been studied. Injections of physiological levels of the tick hormone, 20-hydroxyecdysone (20E), into part-fed (virgin) adult females of the American dog tick, Dermacentor variabilis, attached to the host caused a reduction in density of Rickettsia montanensis in the carcass and an increase in the ovaries compared to buffer-injected controls. This injection initiates yolk protein synthesis and uptake …

Trends And Opportunities In Tick-Borne Disease Geography, Catherine A. Lippi, Sadie J. Ryan, Alexis L. White, Holly D. Gaff, Colin J. Carlson

Biological Sciences Faculty Publications

Tick-borne diseases are a growing problem in many parts of the world, and their surveillance and control touch on challenging issues in medical entomology, agricultural health, veterinary medicine, and biosecurity. Spatial approaches can be used to synthesize the data generated by integrative One Health surveillance systems, and help stakeholders, managers, and medical geographers understand the current and future distribution of risk. Here, we performed a systematic review of over 8,000 studies and identified a total of 303 scientific publications that map tick-borne diseases using data on vectors, pathogens, and hosts (including wildlife, livestock, and human cases). We find that the …

Complete Genome Sequence Of Rickettsia Parkeri Strain Black Gap, Sandor E. Karpathy, Christopher D. Paddock, Stephanie L. Grizzard, Dhwani Batra, Lori A. Rowe, David T. Gauthier

Biological Sciences Faculty Publications

A unique genotype of Rickettsia parkeri, designated R. parkeri strain Black Gap, has thus far been associated exclusively with the North American tick, Dermacentor parumapertus. The compete genome consists of a single circular chromosome with 1,329,522 bp and a G+C content of 32.5%.

Clonally Expanded Alpha-Chain T-Cell Receptor (Tcr) Transcripts Are Present In Aneurysmal Lesions Of Patients With Abdominal Aortic Aneurysm (Aaa), Song Lu, John V. White, Raquel I. Judy, Lisa L. Merritt, Wan Lu Lin, Xiaoying Zhang, Charalambos Solomides, Ifeyinwa Nwaneshiudu, John Gaughan, Dimitri S. Monos, Emilia L. Oleszak, Chris D. Platsoucas

Biological Sciences Faculty Publications

Abdominal aortic aneurysm (AAA) is a life-threatening immunological disease responsible for 1 to 2% of all deaths in 65 year old or older individuals. Although mononuclear cell infiltrates have been demonstrated in AAA lesions and autoimmunity may be responsible for the initiation and account for the propagation of the disease, the information available about the pathogenesis of AAA is limited. To examine whether AAA lesions from patients with AAA contain clonally expanded α-chain TCR transcripts, we amplified by the non-palindromic adaptor-PCR (NPA-PCR)/Vα-specific PCR and/or the Vα-specific PCR these α-chain TCR transcripts. The amplified transcripts were cloned and sequenced. Substantial proportions …

Anti-C1q Autoantibodies Are Frequently Detected In Patients With Systemic Sclerosis Associated With Pulmonary Fibrosis, C. Liaskos, S. Rentouli, T. Simopoulou, A. Gkoutzourelas, G. L. Norman, A. Brotis, I. Alexiou, C. Katsiari, D. P. Bogdanos, L. I. Sakkas

Biological Sciences Faculty Publications

BACKGROUND: Anti-C1q autoantibodies (autoAbs) are associated with systemic lupus erythematosus (SLE) but their presence in other rheumatic diseases has not been adequately investigated.

OBJECTIVE: We aim to assessanti-C1q autoAbs and circulating immune complexes (CICs) in systemic sclerosis (SSc).

METHODS: One hundred twenty four patients with SSc (106 females; median age 59.4 years, range 25-81.4; 75(60.5%) with limited cutaneous SSc[lcSSc], and 49(39.5%) with diffuse cutaneous SSc[dcSSc]), were studied. Twenty-five patients with Sjögren's syndrome (SjS), 29 with rheumatoid arthritis (RA), and 38 patients with systemic lupus erythematosus (SLE) and 53 healthy controls (NC) were also included. ELISAs with high and low salt …

Field Testing Integrated Interventions For Schistosomiasis Elimination In The People's Republic Of China: Outcomes Of A Multifactorial Cluster-Randomized Controlled Trial, Gail M. Williams, Yue-Sheng Li, Darren J. Gray, Zheng-Yuan Zhao, Donald A. Harn, Lisa M. Shollenberger, Sheng-Ming Li, Xinglin Yu, Zeng Feng, Jia-Gang Guo, Jie Zhou, Yu-Lan Dong, Yuan Li, Biao Guo, Patrick Driguez, Marina Harvie, Hong You, Allen G. Ross, Donald P. Mcmanus

Biological Sciences Faculty Publications

Despite significant progress, China faces the challenge of re-emerging schistosomiasis transmission in currently controlled areas due, in part, to the presence of a range of animal reservoirs, notably water buffalo and cattle, which can harbor Schistosoma japonicum infections. Environmental, ecological and social-demographic changes in China, shown to affect the distribution of oncomelanid snails, can also impact future schistosomiasis transmission. In light of their importance in the S. japonicum, lifecycle, vaccination has been proposed as a means to reduce the excretion of egg from cattle and buffalo, thereby interrupting transmission from these reservoir hosts to snails. A DNA-based vaccine (SjCTPI) …

Multistate Survey Of American Dog Ticks (Dermacentor Variabilis) For Rickettsia Species, Joy A. Hecht, Michelle E.J. Allerdice, Elizabeth A. Dykstra, Laura Mastel, Rebecca J. Eisen, Tammi L. Johnson, Holly D. Gaff, Andrea S. Varela-Stokes, Jerome Goddard, Benedict B. Pagac, Christopher D. Paddock, Sandor E. Karpathy

Biological Sciences Faculty Publications

Dermacentor variabilis, a common human-biting tick found throughout the eastern half and along the west coast of the United States, is a vector of multiple bacterial pathogens. Historically, D. variabilis has been considered a primary vector of Rickettsia rickettsii, the causative agent of Rocky Mountain spotted fever. A total of 883 adult D. variabilis, collected between 2012 and 2017 from various locations in 12 states across the United States, were screened for rickettsial DNA. Tick extracts were evaluated using three real-time PCR assays; an R. rickettsii-specific assay, a Rickettsia bellii-specific assay, and a Rickettsia genus-specific …

Lack Of Delayed-Type Hypersensitivity In Striped Bass (Morone Saxatilis), Jessica Shannon Miller

Biological Sciences Theses & Dissertations

Mycobacteriosis is a fatal disease in fishes caused by acid-fast bacteria in the genus Mycobacterium. This disease impacts aquaculture, aquariums, and wild fishes. Unfortunately, there are currently no non-lethal diagnostic tests for mycobacterial infection in fishes. Type IV delayed type hypersensitivity (DTH) responses in vivo and in vitro are currently used for the non-lethal detection of mycobacterial infections in humans and in animals; however, there is little information available on DTH responses in fishes. In this work, we examine in vivo DTH response in Striped Bass (Morone saxatilis), an important U.S. Eastern seaboard fish species, experimentally …

A Variant Pfcrt Isoform Can Contribute To Plasmodium Falciparum Resistance To The First-Line Partner Drug Piperaquine, Satish K. Dhingra, Devasha Redhi, Jill M. Combrinck, Tomas Yeo, John Okombo, Philipp P. Henrich, Annie N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock

Biological Sciences Faculty Publications

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC₉₀) or 50% parasite killing (50% lethal dose [LD₅₀]). This mutation …

Defining The Risk Of Zika And Chikungunya Virus Transmission In Human Population Centers Of The Eastern United States, Carrie A. Manore, Richard S. Ostfeld, Folashade B. Agusto, Holly Gaff, Shannon L. Ladeau

Biological Sciences Faculty Publications

The recent spread of mosquito-transmitted viruses and associated disease to the Americas motivates a new, data-driven evaluation of risk in temperate population centers. Temperate regions are generally expected to pose low risk for significant mosquito-borne disease; however, the spread of the Asian tiger mosquito (Aedes albopictus) across densely populated urban areas has established a new landscape of risk. We use a model informed by field data to assess the conditions likely to facilitate local transmission of chikungunya and Zika viruses from an infected traveler to Ae. albopictus and then to other humans in USA cities with variable human …

Exosomes Serve As Novel Modes Of Tick-Borne Flavivirus Transmission From Arthropod To Human Cells And Facilitates Dissemination Of Viral Rna And Proteins To The Vertebrate Neuronal Cells, Wenshuo Zhou, Michael Woodson, Biswas Neupane, Fengwei Bai, Michael B. Sherman, Kyung H. Choi, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed the presence of purified arthropod/neuronal exosomes …

Selective Mutation Accumulation: A Computational Model Of The Paternal Age Effect, Eoin C. Whelan, Alexander C. Nwala, Christopher Osgood, Stephan Olariu

Biological Sciences Faculty Publications

Motivation: As the mean age of parenthood grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father, but have a deleterious effect in offspring. In this paper we present a computational technique to model the SSC niche in order to examine the phenomenon and draw conclusions across different genes and disorders.

Results: We used a Markov chain to model the probabilities of …

Invasion Of Two Tick-Borne Diseases Across New England: Harnessing Human Surveillance Data To Capture Underlying Ecological Invasion Processes, Katharine S. Walter, Kim M. Pepin, Colleen T. Webb, Holly D. Gaff, Peter J. Krause, Virginia E. Pitzer, Maria A. Diuk-Wasser

Biological Sciences Faculty Publications

Modelling the spatial spread of vector-borne zoonotic pathogens maintained in enzootic transmission cycles remains a major challenge. The best available spatio-temporal data on pathogen spread often take the form of human disease surveillance data. By applying a classic ecological approach-occupancy modelling-to an epidemiological question of disease spread, we used surveillance data to examine the latent ecological invasion of tick-borne pathogens. Over the last half-century, previously undescribed tick-borne pathogens including the agents of Lyme disease and human babesiosis have rapidly spread across the northeast United States. Despite their epidemiological importance, the mechanisms of tick-borne pathogen invasion and drivers underlying the distinct …

Climate, Environmental And Socio-Economic Change: Weighing Up The Balance In Vector-Borne Disease Transmission, Paul E. Parham, Joanna Waldock, George K. Christophides, Deborah Hemming, Folashade Agusto, Katherine J. Evans, Nina Fefferman, Holly Gaff, Abba Gumel, Shannon Ladeau

Biological Sciences Faculty Publications

Arguably one of the most important effects of climate change is the potential impact on human health. While this is likely to take many forms, the implications for future transmission of vector-borne diseases (VBDs), given their ongoing contribution to global disease burden, are both extremely important and highly uncertain. In part, this is owing not only to data limitations and methodological challenges when integrating climate-driven VBD models and climate change projections, but also, perhaps most crucially, to the multitude of epidemiological, ecological and socio-economic factors that drive VBD transmission, and this complexity has generated considerable debate over the past 10-15 …

Epidemic Surveillance Using An Electronic Medical Record: An Empiric Approach To Performance Improvement, Hongzhang Zheng, Holly Gaff, Gary Smith, Sylvain Delisle

Biological Sciences Faculty Publications

BACKGROUNDS: Electronic medical records (EMR) form a rich repository of information that could benefit public health. We asked how structured and free-text narrative EMR data should be combined to improve epidemic surveillance for acute respiratory infections (ARI).

METHODS: Eight previously characterized ARI case detection algorithms (CDA) were applied to historical EMR entries to create authentic time series of daily ARI case counts (background). An epidemic model simulated influenza cases (injection). From the time of the injection, cluster-detection statistics were applied daily on paired background+injection (combined) and background-only time series. This cycle was then repeated with the injection shifted to each …

Patterns Of Gene Expression From Human Costal Cartilage In Relation To The Chest Wall Deformity Pectus Carinatum, Janna E. Grubbs

Biological Sciences Theses & Dissertations

Cartilage deformities within the human chest wall, specifically pectus excavatum (PE) and pectus carinatum (PC) are common (1/400-1/1000) and yet, despite their clinical significance, are some of the least studied disorders pertaining to cartilage [1]. The costal cartilage connecting "false ribs" 8-10 to the sternum is often abnormally grown and can lead to formation of a severely sunken "funnel" chest (PE) or push outwards to form a "pigeon" chest (PC). Both conditions can have impact on the diaphragm, heart, lungs, and psychological function. An established ratio of PE and PC in males to females is 4:1, indicating a sex-linked male …

Novel Architecture Of Costal Cartilage And Implications In Chest Wall Deformities, Anthony J. Asmar

Biological Sciences Theses & Dissertations

Costal cartilage is a type of hyaline cartilage that forms rod-like structures that connect the ribs to the sternum. Deformation of costal cartilage is observed in the chest wall deformities, pectus excavatum and pectus carinatum. Pectus excavatum involves a sternal displacement causing a depression of the chest while pectus carinatum causes a protrusion of the chest. As costal cartilage is not a widely studied tissue, this leaves little knowledge into possible factors involved in the pathogenesis of pectus deformities. Costal cartilage in these deformities has been described as being weakened and may implicate proteoglycans which play an important role in …

Use Of Optimal Control Models To Predict Treatment Time For Managing Tick-Borne Disease, Holly D. Gaff, Elsa Schaefer, Suzanne Lenhart

Biological Sciences Faculty Publications

Tick-borne diseases have been on the rise recently, and correspondingly, there is an increased interest in implementing control measures to decrease the risk. Optimal control provides an ideal tool to identify the best method for reducing risk while accounting for the associated costs. Using a previously published model, a variety of frameworks are assessed to identify the key factors influencing mitigation strategies. The level and duration of tick-reducing efforts are key metrics for understanding the successful reduction in tick-borne disease incidence. The results show that the punctuated nature of the tick's life history plays a critical role in reducing risk …

An Epidemiological Model Of Rift Valley Fever, Holly D. Gaff, David M. Hartley, Nicole P. Leahy

Biological Sciences Faculty Publications

We present and explore a novel mathematical model of the epidemiology of Rift Valley Fever (RVF). RVF is an Old World, mosquito-borne disease affecting both livestock and humans. The model is an ordinary differential equation model for two populations of mosquito species, those that can transmit vertically and those that cannot, and for one livestock population. We analyze the model to find the stability of the disease-free equlibrium and test which model parameters affect this stability most significantly. This model is the basis for future research into the predication of future outbreaks in the Old World and the assessment of …