bluuebunny/crossref_metadata_2025_split huggingface dataset:
Internal State: Dynamic, Interconnected Communication Loops Distributed Across Body, Brain, and Time
Authors: Kanwal Jessleen K , Coddington Emma , Frazer Rachel , Limbania Daniela , Turner Grace , Davila Karla J , Givens Michael A , Williams Valarie , Datta Sandeep Robert , Wasserman Sara 
Published: June 2021

Synopsis
Internal state profoundly alters perception and behavior. For example, a starved fly may approach and consume foods that it would otherwise find undesirable. A socially engaged newt may remain engaged in the presence of a predator, whereas a solitary newt would otherwise attempt to escape. Yet, the definition of internal state is fluid and ill-defined. As an interdisciplinary group of scholars spanning five career stages (from undergraduate to full professor) and six academic institutions, we came together in an attempt to provide an operational definition of internal state that could be useful in understanding the behavior and the function of nervous systems, at timescales relevant to the individual. In this perspective, we propose to define internal state through an integrative framework centered on dynamic and interconnected communication loops within and between the body and the brain. This framework is informed by a synthesis of historical and contemporary paradigms used by neurobiologists, ethologists, physiologists, and endocrinologists. We view internal state as composed of both spatially distributed networks (body–brain communication loops), and temporally distributed mechanisms that weave together neural circuits, physiology, and behavior. Given the wide spatial and temporal scales at which internal state operates—and therefore the broad range of scales at which it could be defined—we choose to anchor our definition in the body. Here we focus on studies that highlight body-to-brain signaling; body represented in endocrine signaling, and brain represented in sensory signaling. This integrative framework of internal state potentially unites the disparate paradigms often used by scientists grappling with body–brain interactions. We invite others to join us as we examine approaches and question assumptions to study the underlying mechanisms and temporal dynamics of internal state.
Bioeconomic benefits of managing fishing effort in a coexisting small- and large-scale fishery game
Authors: de Azevedo Eric Zettermann Dias , Pintassilgo Pedro , Dantas David Valença , Daura-Jorge Fábio Gonçalves 
Published: June 2021

Abstract
Fishing systems provide employment, income generation, poverty alleviation, and food security. The coexistence of small-scale fisheries (SSFs) and large-scale fisheries (LSFs) increases management complexity. Management actions have ecological and social implications that must be addressed carefully. We applied a bioeconomic game-theoretical model to the four-gear mullet fishery in southern Brazil—one industrial LSF (purse seine) and three artisanal SSFs (gillnet, beach seine, and drift net). All fishing gears target adult individuals during mullet's reproductive migration. First, we explored whether the current fishing efforts of all fishing gears could persist over time. Second, we investigated their interactions through a non-cooperative game. Finally, we studied the response of these interactions when fishing effort was restricted. We found that when the current fishing effort was maintained, the stock reduced to 26.4% of its capacity in 25 years. In addition, under non-cooperation, the traditional beach seine fleet exited the fishery. Interestingly, the constrained scenario had a coexistence output with increasing values for the final stock size and the per capita labour income, suggesting that limiting fishing effort can maintain all fishing gears in the fishery with social and ecological benefits.
Doubling Down: The Danger of Disclosing Secret Action
Authors: Otto Jacob , Spaniel William 
Published: June 2021

Abstract
When an actor catches a state taking an objectionable secret action, it faces a dilemma. Exposing the action could force unresolved states to terminate the behavior to save face. However, it could also provoke resolved states to double down on the activity now that others are aware of the infraction. We develop a model that captures this fundamental trade-off. Three main results emerge. First, the state and its opponent may engage in a form of collusion—opponents do not expose resolved states despite their distaste for the behavior. Second, when faced with uncertainty, the opponent may mistakenly expose a resolved type and induce escalation, leading the opponent to have ex post regret. Finally, as the strength of secret action increases, states may engage in it less often. This counterintuitive result is a consequence of the opponent's greater willingness to expose, which deters less resolved types.
Towards a knowledge base of medieval and renaissance geographical Latin works: The IMAGO ontology
Authors: Bartalesi Valentina , Metilli Daniele , Pratelli Nicolò , Pontari Paolo 
Published: June 2021

Abstract
In this article we present the first achievement of the Index Medii Aevi Geographiae Operum (IMAGO)—Italian National Research Project (2020–23), that is, the ontology we have created in order to formally represent the knowledge about the geographical works written in Middle Ages and Renaissance (6th–15th centuries). The IMAGO ontology is derived from a strict collaboration between the Institute of Information Science and Technologies (ISTI) of the Italian National Research Council (CNR) and the scholars who are involved in the project, who have supported ISTI-CNR in defining a conceptualization of the domain of knowledge. Following the re-use logic, we have selected as reference ontologies the International Committee on Documentation CRM vocabulary and its extension FRBRoo, including its in-progress reformulation, LRMoo. This research is included in a wider project context whose final aim is the creation of a knowledge base (KB) of Latin geographic literature of the Middle Ages and Renaissance Humanism in which the data are formally represented following the Linked Open Data paradigm and using the Semantic Web languages. At the end of the project, this KB will be accessed through a Web application that allows retrieving and consulting the collected data in a user-friendly way for scholars and general users, e.g. tables, maps, CSV files.
Comparative effects of combined use of alcohol with cannabis and tobacco on testicular function in rats
Authors: Nwonuma Charles Obiora , Osemwegie Osarenkhoe Omorefosa , Irokanulo Emenike Onyebum , Alejolowo Omokolade Oluwaseyi , Kayode Omowumi Titilola , Olaolu Tomilola Debby , Ada Adakole Sylvanus , Rotimi Damilare Emmanuel , Maimako Roltdelmwa Filibus , Adedayo Adeyinka Samuel , Ojo Oluwafemi Adeleke 
Published: June 2021

AbstractAlcoholism has been linked to problems with male reproductive function. The combined effects of alcohol, cannabis, and tobacco were compared in this study. A total of 35 rats were assigned randomly into seven groups A–G: animals in A were administered distilled water. Animals in B–G were either administered alcohol orally (30 ml 40% alcohol) or exposed to smoke from ignited tobacco (exposure to smoke from 0.7 g tobacco for 5 min) or cannabis (exposure to smoke from 0.7 g tobacco and cannabis for 5 min): B (orally administered alcohol), C (exposed to the smoke from tobacco), D (exposed to smoke from cannabis), E (treated with alcohol and exposed to smoke from tobacco), F (treated with alcohol and exposed to smoke from cannabis), G (treated with alcohol and exposed to smokes from tobacco and cannabis). Assays were carried on the testicular homogenate after a 14-day treatment. There was a significant increase in activity of alkaline phosphatase (P ≤ 0.05), concentrations of cholesterol, glutathione reductase, and malondialdehyde in treated rats by the co-administration of alcohol with cannabis and tobacco compared with the control group. The combined treatment also caused degeneration and morphological distortions of testicular cells. The biochemical and histoarchitectural change was due to oxidative damage attributable to the synergistic effects. The high binding energy of tetrahydrocannabinol ligand to prostate acid phosphatase may be a prediction that the ligand can have an inhibitory effect on the function of enzymes in the prostate.
Phylodynamics reveals the role of human travel and contact tracing in controlling the first wave of COVID-19 in four island nations
Authors: Douglas Jordan , Mendes Fábio K , Bouckaert Remco , Xie Dong , Jiménez-Silva Cinthy L , Swanepoel Christiaan , de Ligt Joep , Ren Xiaoyun , Storey Matt , Hadfield James , Simpson Colin R , Geoghegan Jemma L , Drummond Alexei J , Welch David 
Published: June 2021

Abstract
New Zealand, Australia, Iceland, and Taiwan all saw success in controlling their first waves of Coronavirus Disease 2019 (COVID-19). As islands, they make excellent case studies for exploring the effects of international travel and human movement on the spread of COVID-19. We employed a range of robust phylodynamic methods and genome subsampling strategies to infer the epidemiological history of Severe acute respiratory syndrome coronavirus 2 in these four countries. We compared these results to transmission clusters identified by the New Zealand Ministry of Health by contact tracing strategies. We estimated the effective reproduction number of COVID-19 as 1–1.4 during early stages of the pandemic and show that it declined below 1 as human movement was restricted. We also showed that this disease was introduced many times into each country and that introductions slowed down markedly following the reduction of international travel in mid-March 2020. Finally, we confirmed that New Zealand transmission clusters identified via standard health surveillance strategies largely agree with those defined by genomic data. We have demonstrated how the use of genomic data and computational biology methods can assist health officials in characterising the epidemiology of viral epidemics and for contact tracing.
The Dynamic Nucleotide Selection Mechanism of DNA Polymerase I at Atomic Resolution
Authors: Wu Eugene Y. , Miller Bill R. , Parish Carol A. 
Published: June 2021

Replicative DNA polymerases use complex induced fit mechanisms to distinguish substrates complementary to the template from mismatches with remarkable speed and accuracy. The transient conformations and their order in the mechanism underly the speed and accuracy of polymerases, yet are difficult to characterize due to the sub‐millisecond time scales of the transitions. We employed microsecond scale, all‐atom, explicit waters molecular dynamics to characterize and visualize the conformational changes that occur when DNA polymerase I, large fragment, from Bacillus stearothermophilus encounters a complementary dCTP or a mismatched dTTP opposite a template dG. The dCTP and the Mg2+ cofactor immediately formed a stable base pair with dG and induced fluctuations of the mobile fingers subdomain between the open conformation and a state intermediate between open and closed. The enzyme closed only upon the binding of a second cation to the active site, followed by a rotation of a conserved histidine towards the 3′‐OH of the growing primer strand. We speculate this is the deprotonation step that initiates catalysis. In the presence of the mismatched dTTP‐Mg2+, a weak base pair forms with dG, but quickly breaks, leading to near dissociation of the dTTP during the 3μs simulation. These simulations detail the complex polymerase mechanism and provide structural explanations for the behavior and high fidelity of dynamic DNA polymerases during nucleotide selection.Support or Funding InformationThe authors would like to acknowledge the Jeffress Trust Awards Program in Interdisciplinary Research for funding, as well as the University of Richmond for computing resources.This work also used Extreme Science Engineering Discovery Environment (XSEDE) allocations TG‐MCB140003 and TG‐MCB140073, which are supported by National Science Foundation grant number OCI‐1053575. Additional computing resources were utilized as part of the MERCURY Consortium supported by NSF grant number CHE‐1229354
UNDERSTANDING A FUNDAMENTAL FORCE IN PROTEIN FOLDING: TUNING THE n ‐‐> > π* INTERACTION VIA DESIGNED PEPTIDES
Authors: Wenzell Nicole A , Ganguly Himal K , Pandey Anil K , Yap Glenn P.A , Zondlo Neal J 
Published: June 2021

An n‐‐>π* interaction is a local interaction that orders two consecutive residues by delocalizing the lone pair of electrons from oxygen of the donor carbonyl to the antibonding orbital of the acceptor carbonyl carbon. This interaction is a recent discovery that gives insight into the inherent biases that proteins have to drive them to their folded state. By changing the electronics of the donor carbonyl on model proline‐based peptides, we can tune the strength of this n‐‐>π* interaction.Proline can readily populate both the trans and cis conformations in a peptide bond. The n‐‐>v* interaction is shown to stabilize the trans conformation. Thus, in our model system the equilibrium constant of trans‐cis isomerization (Ktrans/cis) acts as a readout for the strength of the n‐‐>π* interaction. Greater electron donation on the donor carbonyl causes a stronger interaction, resulting in higher Ktrans/cis values. The electronics of the donor carbonyl in the model peptides were modulated by synthesizing a series of derivatives with varying electron‐donating capabilities on the donor carbonyl.The series of derivatives synthesized were selected in order to compare their electron donating capabilities to their n‐‐>π* interaction strength. The derivatives synthesized for analysis were, Boc, pivaloyl, formyl, acetyl, monochloroacetyl, dichloroacetyl, trichloroacetyl and trifluoroacetyl. These successfully synthesized derivatives provide a range of electronic character to be analyzed for the strength of the n‐‐>π* interaction in each compound.The determination of the strength of the n‐‐>π* interaction was accomplished through combined analysis via 1H and 13C NMR and X‐ray crystallography. NMR analysis provides the Ktrans/cis values for each derivative and thus the strength of the nàπ* interaction. Electron donation involved in the n‐‐>π* interaction is seen via the chemical shifts of the 13C NMR. The chemical shift of the acceptor carbonyl moves downfield with stronger electron‐donating substituents, while carbonyls uninvolved in the interaction remain constant. X‐ray crystallography of the model peptides reveals insights into the n‐‐>π* interaction as it indicates the distance and angles of the interaction. Specifically, the more electron donating character of the acetyl compared to the formyl group results in a 0.3Å shorter distance (3.3‐3.0Å) and an angle (115°vs 90°) that more closely resembles an ideal nucleophilic attack (109.5°). The comparison of the Ktrans/cis values, the carbonyl chemical shifts, and the angles and distances of the donor‐acceptor carbonyl pair serve as direct readouts for the strength of the n‐‐>π* interaction, which varies depending on the electron donating character of the donor carbonyl.Support or Funding InformationThe David Plastino Scholars program at the University of Delaware as well as the National Science Foundation.
Bioengineering Proteoglycan‐based Matrices For Blood Contacting Applications
Authors: Lord Megan , Chuang Christine , Rnjak‐Kovacina Jelena , Cheng Bill , Lyons Guy , Whitelock John 
Published: June 2021

Proteoglycans and their glycosaminoglycan chains are functional components of the extracellular matrix that modulate interactions with other extracellular matrix molecules, as well as with cells and growth factors. Perlecan is an abundant proteoglycan in the vascular basement membrane and contains a C‐terminal domain V (DV) with one glycosaminoglycan attachment site and an α2β1 integrin binding site. Perlecan can only be obtained in low abundance from natural sources, thus alternative sources are needed for therapeutic applications. The aim of this research was to bioengineer DV and to incorporate it into biomaterials for blood‐contacting applications.Human DV was expressed in the human embryonic kidney cell line, HEK‐293 and purified by immunoaffinity chromatography and biochemically characterized with respect to protein core, glycosaminoglycan structure and yield. Human primary endothelial cell, smooth muscle cell and platelet adhesion were assessed.DV was produced as two populations decorated with either chondroitin sulfate or heparan sulfate. The level of heparan sulfate substitution was increased by culturing the cells with higher glucose concentrations in the medium while there was no effect on the level of chondroitin sulfate. DV was produced with a yield of 2 mg/L, which is a 2.5 fold increase in the yield of endothelial‐derived perlecan.The proteoglycan forms of DV were effective in promoting endothelial, but not smooth muscle cell or platelet adhesion. In the absence of glycosaminoglycans DV supported the adhesion of endothelial cells and platelets via integrin α2β1. However, while smooth muscle cells adhere to perlecan in the absence of glycosaminoglycan chains, these cells did not adhere to DV in the absence of glycosaminoglycans. This suggests that the proteoglycan forms of DV have potential roles in encouraging endothelialization of materials while inhibiting unwanted activities associated with platelet and smooth muscle cell adhesion. We have shown this to be the case for the full length perlecan when trialed in an ovine vascular graft model.We are currently developing methods to combine DV with various biomaterials including a silk fibroin substrate through various chemical crosslinking methods. Early work in this area suggests that we can fine tune how both the protein and glycosaminoglycan components of DV are presented to maintain the vascular cell‐selective activities of DV.Support or Funding InformationFunding provided by the Australian Research Council
Evaluation of Compounds that Inhibit Fatty Acid Uptake in Mice
Authors: Taylor Samuel , Saini Nipun , Montefusco David , Black Paul , DiRusso Concetta 
Published: June 2021

Lipotoxicity is characterized by apoptosis due to the toxic spillover of fatty acids from adipocytes into non‐adipose tissue. Adipocytes function to store fat and then release free fatty acids during fasting and starvation. In obesity, however, storage capacity in adipocytes becomes limiting and circulating triglycerides and free fatty acids are elevated, which can lead to accumulation in non‐adipose tissue. This can result in dysfunction, especially in the liver, muscle and pancreas. The purpose of this research is to measure the degree of fatty acid uptake inhibition in mouse models by two long‐chain fatty acid transport protein inhibitors, designated lipofermata and grassofermata in previous work. 13C18‐labeled oleic acid provided in flaxseed oil was delivered to mice by gavage following administration of compound or vehicle in flaxseed oil and the animals were sacrificed and blood collected by cardiac puncture. Plasma, tissue, and fecal levels of 13C18‐oleate were assessed by gas chromatography/mass spectrometry (GC/MS) of fatty acid methyl ester preparations (FAMES) with selective ion monitoring (SIM). We found 13C18‐oleate uptake to be inhibited by approximately 40% (grassofermata) and 75% (lipofermata) in mice sacrificed six hours after labeled oleate gavage. This work demonstrates effective inhibition of these compounds in short‐term studies and calls for further characterization of these inhibitors in long‐term investigations, which may ultimately have implications as pharmaceutical therapies.Support or Funding InformationArnold and Mabel Beckman Foundation, USDA Hatch and NIFA
Oligomerization of wild‐type fumarase and a mutant associated with fumarate hydratase deficiency
Authors: Bulku Artemisa , Aleksanyan Naira , Berkmen Melanie 
Published: June 2021

Fumarase, or fumarate hydratase, is an enzyme that participates in the citric acid cycle and catalyzes the reversible hydration of fumarate to malate. Homozygous germline mutations in FH, the human fumarate hydratase gene, are linked to fumarate hydratase deficiency (FHD). Clinical features of this inborn error of metabolism include encephalitis, seizures, brain abnormalities, and developmental delay. Fumarase protein sequences are evolutionarily conserved, with human FH and Escherichia coli FumC sharing a stunning 59% amino acid sequence identity. Crystallographic analyses of E. coli and yeast fumarase have revealed that fumarase is homotetrameric, with two substrate binding sites, called the A‐ and B‐sites. Previously, the Weaver lab used X‐ray crystallography and kinetic experiments to investigate wild‐type FumC and FumC (E315Q), a clinically relevant mutant associated with FHD (Estevez, Skarda, Spencer, Banaszak, and Weaver, Protein Science 11:1552–7, 2002). They found that the E315 residue is conserved, lies within the A‐site, and is critical for catalysis. In this study, we purified both proteins and used fumarase assays and blue native PAGE (BN‐PAGE) to analyze their enzymatic activity and oligomerization states, respectively. Consistent with the findings from Estevez et al., we found that the E315Q mutant has greatly reduced enzymatic activity but is able to form tetramers. In future studies, we plan on analyzing other fumarase variants that have not been previously characterized.Support or Funding InformationNSF
Nutrient Intakes from Restaurants among U.S. Children Age 1–2 Years
Authors: Jarvis Ashley B. , Clemens John C. , Rhodes Donna G. , Moshfegh Alanna J. 
Published: June 2021

Nationally representative one‐day dietary data of U.S. children age 1–2 years, excluding breast‐fed, (n=469) participating in What We Eat in America, NHANES 2011–2012 were analyzed to assess nutrient intakes from foods and beverages obtained from restaurants. The 5‐step USDA Automated Multiple‐Pass Method was used to collect the dietary data through a 24‐hour recall from a proxy knowledgeable about the child's intake. The source of each item (where obtained) was provided by the proxy. Restaurants include full service and quick service establishments as well as: cafeteria, not at school; sport/entertainment facility; vending truck. Restaurant consumers were defined as individuals who reported, on the intake day, at least one food or beverage item from a restaurant. On any given day, 28% of 1 year‐olds and 40% of 2 year‐olds were restaurant consumers. Among consumers, the contribution of restaurant items to total daily energy intake was 27±1.6%. Contribution of restaurant items to total daily intake of macronutrients was 28±1.6% for protein, 23±2.0% for carbohydrate, and 32±1.6% for total fat. Compared to energy and macronutrient intakes, the contribution was greater for sodium; on the day consumed, restaurant items contributed 34±1.6% to total daily sodium intake. For calcium, potassium, and lycopene restaurant items contributed 17±1.8, 21±1.6, and 44±6.2%, respectively to total daily nutrient intakes. Restaurant foods and beverages contributed over a fourth of calories and a third of sodium to the diets of 1–2 year‐olds, highlighting the importance of their consideration when making dietary recommendations or intervention strategies.Support or Funding InformationThis study was funded by the USDA Agricultural Research Service.