bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenomic Analysis Reveals Dispersal-Driven Speciation and Divergence with Gene Flow in Lesser Sunda Flying Lizards (Genus Draco)
Authors: Reilly Sean B , Stubbs Alexander L , Arida Evy , Karin Benjamin R , Arifin Umilaela , Kaiser Hinrich , Bi Ke , Iskandar Djoko T , McGuire Jimmy A 
Published: June 2021

Abstract
The Lesser Sunda Archipelago offers exceptional potential as a model system for studying the dynamics of dispersal-driven diversification. The geographic proximity of the islands suggests the possibility for successful dispersal, but this is countered by the permanence of the marine barriers and extreme intervening currents that are expected to hinder gene flow. Phylogenetic and species delimitation analyses of flying lizards (genus Draco) using single mitochondrial genes, complete mitochondrial genomes, and exome-capture data sets identified 9–11 deeply divergent lineages including single-island endemics, lineages that span multiple islands, and parapatrically distributed nonsister lineages on the larger islands. Population clustering and PCA confirmed these genetic boundaries with isolation-by-distance playing a role in some islands or island sets. While gdi estimates place most candidate species comparisons in the ambiguous zone, migration estimates suggest 9 or 10 species exist with nuclear introgression detected across some intra-island contact zones. Initial entry of Draco into the archipelago occurred at 5.5–7.5 Ma, with most inter-island colonization events having occurred between 1–3 Ma. Biogeographical model testing favors scenarios integrating geographic distance and historical island connectivity, including an initial stepping-stone dispersal process from the Greater Sunda Shelf through the Sunda Arc as far eastward as Lembata Island. However, rather than reaching the adjacent island of Pantar by dispersing over the 15-km wide Alor Strait, Draco ultimately reached Pantar (and much of the rest of the archipelago) by way of a circuitous route involving at least five overwater dispersal events. These findings suggest that historical geological and oceanographic conditions heavily influenced dispersal pathways and gene flow, which in turn drove species formation and shaped species boundaries. [Biogeography; genomics, Indonesia; lizards; phylogeography; reptiles]
Clinical Effects and Predictive Factors Affecting the Clinical Severity of Scorpion Envenomations in Western Turkey
Authors: Çelik Elif , Çağlar Aykut , Çelik Serkan Fazlı 
Published: June 2021

Abstract

Background
Scorpion envenomation is a common medical emergency in many countries, including Turkey. Severe systemic symptoms occur more easily in children and mortality rates are higher. The aim of this study is to describe the clinical effects and predictive factors affecting the clinical severity of scorpion envenomations in Western Turkey.

Methods
Two hundred one children (138 mild cases, 34 moderate, and 29 severe) with scorpion envenomation aged between 1 month and −17 years were included in the study. The patients’ demographic and laboratory characteristics were compared among clinical severity subgroups.

Results
The patients’ median age was 7 (4–11) years. The median age of the severe group was significantly lower than that of the mild and moderate groups (p &lt; 0.001). Seventeen patients (8.5%) developed myocarditis, while no pulmonary edema was observed in any case. Leukocyte, neutrophil and platelet (PLT) counts, and plateletcrit (PCT) and glucose levels increased significantly with the severity of envenomation (p &lt; 0.001). PLT counts and PCT levels exhibited positive correlation with leukocyte and neutrophil counts (p &lt; 0.001, r = 0.781, r = 0.638, r = 0.772, and r = 0.629, respectively). Supraventricular tachycardia developed in 1 (5.9%) patient, and dilated cardiomyopathy in another (5.9%). No mortality occurred in any case.

Conclusion
Increased PLT counts and PCT levels may be helpful in evaluating clinical severity in patients with scorpion sting envenomation. The possibility of myocarditis development in children should be remembered and cardiac enzymes should be checked, even if patients are asymptomatic and cardiac enzymes are normal on admission.
Increased virulence of Italian infectious hematopoietic necrosis virus (IHNV) associated with the emergence of new strains
Authors: Abbadi Miriam , Gastaldelli Michele , Pascoli Francesco , Zamperin Gianpiero , Buratin Alessandra , Bedendo Giulia , Toffan Anna , Panzarin Valentina 
Published: June 2021

Abstract
Infectious hematopoietic necrosis virus (IHNV) is the causative agent of IHN triggering a systemic syndrome in salmonid fish. Although IHNV has always been associated with low levels of mortality in Italian trout farming industries, in the last years trout farmers have experienced severe disease outbreaks. However, the observed increasing virulence of IHNV is still based on empirical evidence due to the poor and often confounding information from the field. Virulence characterization of a selection of sixteen Italian isolates was performed through in vivo challenge of juvenile rainbow trout to confirm field evidence. The virulence of each strain was firstly described in terms of cumulative mortality and survival probability estimated by Kaplan–Meier curves. Furthermore, parametric survival models were applied to analyze the mortality rate profiles. Hence, it was possible to characterize the strain-specific mortality peaks and to relate their topology to virulence and mortality. Indeed, a positive correlation between maximum mortality probability and virulence was observed for all the strains. Results also indicate that more virulent is the strain, the earliest and narrowest is the mortality peak. Additionally, intra-host viral quantification determined in dead animals showed a significant correlation between viral replication and virulence. Whole-genome phylogeny conducted to determine whether there was a relation between virulence phenotype and IHNV genetics evidenced no clear clustering according to phenotype. Moreover, a root-to-tip analysis based on genetic distances and sampling date of Italian IHNV isolates highlighted a relevant temporal signal indicating an evolving nature of the virus, over time, with the more virulent strains being the more recent ones. This study provides the first systematic characterization of Italian IHNV’s virulence. Overall results confirm field data and point out an abrupt increase in IHNV virulence, with strains from 2015–2019 showing moderate to high virulence in rainbow trout. Further investigations are needed in order to extensively clarify the relation between evolution and virulence of IHNV and investigate the genetic determinants of virulence of this viral species in rainbow trout.
Visualizing Biochemistry: The Implementation of Biomolecular Visualization and Structure‐Function Conceptual Game‐based Card Sorting Activities
Authors: Bates Alison , Terrell Cassidy R. 
Published: June 2021

Biochemistry, at the undergraduate level, is in a distinctive position to unveil misconceptions as the topics covered are abstract and require recollection of content from prior STEM courses. These components, when compounded with myriad of representations, likely exceed the cognitive load of the students and therefore propagate misconceptions. Current research suggests that undergraduate students learn visual literacy skills indiscriminately throughout his/her academic career. Therefore, we propose that direct instruction of biomolecular visualization will reduce the cognitive load and increase conceptual understanding.This study aims to answer the questions: Do targeted interventions improve accuracy and precision of card sorting across the semester? and Do targeted interventions increase conceptual understanding of structure and function across the semester? Preliminary findings from pre‐ and post‐ “free sort” card sorting activities in control semesters provided evidence for the design of a series of interventions. These interventions aim to increase the visual literacy of undergraduate biochemistry students while simultaneously increasing structure‐function content understanding using game‐based card sorting activities. Game‐based learning is used to increase motivation, comprehension, and sense of achievement in students. Three interventions were designed and implemented into the biochemistry curriculum for fall 2017. Student responses from these activities and the matching card section on exams were analyzed in addition to the pre‐ and post‐”free sort” card sorting activities. These data are compared to control groups from two previous semesters. Furthermore, the data are analyzed using qualitative inferential, quantitative inferential, and descriptive statistical analysis. Refinement of the interventions will continue into future semesters of biochemistry with the intention of setting a standard of targeted instruction of visual literacy skills.Support or Funding InformationThis project is partially supported by the National Science Foundation under award number DUE1323414 to Milwaukee School of Engineering.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Using developmental rate variation to establish a fine‐grained sequence of ossification center differentiation
Authors: Flaherty Kevin V. , Halmi Caroline , Richtsmeier Joan 
Published: June 2021

Mouse embryos from inbred strains exhibit a large range of phenotypic diversity, despite tight controls placed on genetic variation and environmental conditions. Individuals vary in terms of body size and the progress of developmental morphology, even within litters. This indicates that individual embryos develop at different rates. Staging atlases such as those developed by Kaufman and Theiler provide details of the morphological features and developmental processes evident on successive days of development, but do not offer a systematic method for determining if two embryos represent similar developmental stages within more fine‐grained time periods. To ensure that studies of developmental processes like tissue interactions and gene expression events that occur within restricted periods of a few hours are not confounded by inter‐individual variation in rates of development, precise temporal control is needed to sequentially order and contextualize data collected from individual embryos. We collected and compared temporal sequences of ossification center appearance and development using two measures of individual development: size, measured as crown‐rump length, and shape, using the eMOSS staging system (http://www.limbstaging.crg.es/) that generates estimates of individual ages based on the 2D outline of the hindlimb.Using crown‐rump length and the eMOSS system, we demonstrate significant developmental variation within litters, and significant disparity between an embryo's age based on the age at collection and age generated from eMOSS. Using eMOSS, we are able to elucidate the sequence of bone development in unprecedented detail. We recorded the appearance of ossification centers by scoring the presence of the critical osteoblast differentiation gene Osterix in OSX‐GFP mice sacrificed at 6 hour increments from E12.0 to E15.0 and scored the appearance of calcified bone by staining C57Bl/6 embryos between E14.0 and E16.0 with calcein. We improved the understanding of the temporal sequence and precise timing of these developmental events by generating an ossification center development sequence that details the appearance of bones according to the overall body size, and more importantly, the developmental hour at which they appeared.Support or Funding InformationThis work is supported in part by the NIH: Craniosynostosis Network P01HD078233 & R01DE018500, R01DE022988; NSF BCS‐1650824; and the Burroughs Wellcome Fund.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Early‐Life Sickness May Predispose Individuals to Behavioral Changes Following Gut Dysbiosis in Adulthood
Authors: Sylvia Kristyn E. , Deyoe Jessica E. , Demas Gregory E. 
Published: June 2021

Although it is well‐established that the immune system plays an important role in the development of physiology and behavior, the gut microbiome has recently become of interest in the study of developmental origins of behavior. Some studies suggest that the effects of early‐life immune activation may not occur until a secondary stressor is introduced, though the precise nature and timing of the stressor may be critical in the response. In order to test the hypothesis that early‐life immune stress makes an individual more vulnerable to future insults, we mimicked an early‐life infection by injecting pups at postnatal day 3 and 5 with lipopolysaccharide (LPS; cell wall component of gram‐negative bacteria) or saline, and subsequently exposed the same animals to antibiotic treatment (known to influence microbial community composition ad behavior) or water in adulthood. We tracked physiology across development, and paired males and females with a novel individual of the same sex in adulthood to score behavior before antibiotic treatment, immediately following treatment, and after recovery from antibiotics. LPS‐treated females exhibited impaired reproductive physiology and function in adulthood (e.g., smaller ovaries and abnormal estrous cycles), and female and male gut microbial communities were strongly affected by antibiotic treatment in adulthood, but only slightly affected by postnatal LPS alone. Interestingly, LPS‐treated males exhibited more robust changes in their behavioral response following adult antibiotic treatment, including decreased investigation and increased grooming. These data suggest that males may be more vulnerable than females to behavioral abnormalities after being predisposed to an immune challenge early in life. Collectively, these results provide evidence that some of the sex‐specific behavioral consequences of a stressor may not transpire until an individual is faced with a secondary stressor, and the context in which an individual is exposed can greatly influence the response.Support or Funding InformationNational Institute of Child Health and Human Development (T32HD49336); National Science Foundation, Division of Integrative Organismal Systems (1656414); and Indiana UniversityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Identifying C‐Mannosylated Proteins in RAW264.7 Cells
Authors: Kegley Nicholas Ryan , Boober Karli , Ito Atsuko , Takeuchi Megumi , Haltiwanger Robert S , Rakus John 
Published: June 2021

C‐mannosylation is a specific type of glycosylation in which α‐mannose is covalently bound to the C2 atom of a tryptophan via a carbon‐carbon bond. Presently, it is known to occur on proteins that contain the W‐x‐x‐W‐x‐x‐W/C motif found within the Thrombospondin Type‐1 Repeat (TSR), with ‘x’ denoting any other amino acid. C‐mannosylation has been implicated in a few cellular functions, including protein secretion and type I cytokine receptor function. Previous research has shown that exogenous C‐mannosylated peptides derived from TSR containing proteins upregulate the production of the pro‐inflammatory cytokine Tumor Necrosis Factor alpha (TNF‐α) in RAW264.7 macrophage cells. This upregulation is substantially increased in the presence of Hsc70. When these peptides are internalized by RAW264.7 cells, a binding interaction occurs between the two proteins, which also correlates with increased TNF‐α levels. With the knowledge that exogenous C‐mannosylated peptides and Hsc70 can influence cytokine production, this study has focused on identifying endogenous C‐mannosylated proteins in RAW264.7 cells that interact with Hsc70. The potential of a naturally occurring interaction between these two proteins could elucidate the importance of C‐mannosylation in the innate immune response. Through a Hsc70 co‐immunoprecipitation, a potentially C‐mannosylated protein has been identified in Junctophilin‐1 (JPH1). JPH1 forms a junctional membrane complex (JMC) between the endoplasmic reticulum and plasma membrane of excitable cells, facilitating communication between calcium ion release channels. When comparing the nano‐LC MS/MS results for JPH1 against a mouse database, 69 separate PSMs were shown where JPH1 carries a hexose. MS/MS data suggests that the hexose appears on a single tryptophan in a peptide bearing the sequence: E‐G‐E‐W‐A‐N‐N‐K. This indicates that JPH1 may be an example of non‐canonical C‐mannosylation. To further explore the status of JPH1 as a C‐mannosylated protein, the protein was overexpressed in HEK293T cells. This experiment showed that JPH1 was not C‐mannosylated in HEK293T cells. Noting the lack of modification, RTPCR was performed with both RAW264.7 and HEK293T RNA. These experiments showed that all four DPY19L homologs were expressed in HEK293T cells, while only DPY19L1 and L4 were expressed in RAW cells. Further work is being conducted to overexpress JPH1 in RAW264.7 cells to determine why, or if, JPH1 is C‐mannosylated in this particular cell line.Support or Funding InformationThis work was supported by NSF grant OIA‐1738707.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Comparing the susceptibility of genetically modified mice to intoxication by organophosphorus nerve agents
Authors: Cadieux C. Linn , Guzman Juanita J. , Corun Charlene M. , Rausa Rebecca C. , Lenz David E. , Cerasoli Douglas M. 
Published: June 2021

To examine the contributions of butyrylcholinesterase (BuChE) and paraoxonase 1 (PON1) to the gestalt resistance of mice to organophosphorus (OP) nerve agents, we determined the LD50s of GB, GD, and VX in mice deficient in BuChE, PON1, or both; likewise, mice expressing either human PON1 or the mutant G117H human BuChE were tested. The results indicate that the absence of BuChE, PON1, or both does not enhance susceptibility to GB or GD, and has only a modest effect on susceptibility to VX (statistically significant only for female mice). The transgenic expression of human PON1 or G117H BuChE did not enhance resistance to OP intoxication. LD50s varied by as much as 50% between mice of different backgrounds, independent of the presence of knockout or transgene alleles. Female mice of all backgrounds were more resistant to OP intoxication than corresponding males. The results suggest that in mice, neither BuChE nor PON1 plays a substantial role in resistance to OP intoxication. Further, for these enzymes to provide protection if administered as exogenous bioscavengers, they must be present at concentrations higher than normally found in mice.This work was supported by funding from DTRA.
The relation between serum xanthophylls, fatty acids, macular pigment and cognitive function in the Health ABC Study
Authors: Renzi Lisa Marie , Iannaccone Alessandro , Johnson Elizabeth , Kritchevsky Stephen 
Published: June 2021

Xanthophylls lutein and zeaxanthin (L, Z) and ù‐3 fatty acids (FAs), are optimally positioned in retina and cortex to protect from oxidative damage. Research suggests that this placement in retinal tissue is related to reduced risk for acquired retinal diseases and improved visual function (e.g., reduced glare disability, scotopic noise). Whether L, Z and FAs in the cortex are capable of similarly influencing cognitive function (CF) is unknown. The purpose of this investigation was to determine the relation between L, Z and FAs and CF in a healthy cohort of older adults. 118 subjects in the Memphis, TN area, aged 76–85 yrs, with approx. equal numbers of males/females. Retinal L, Z levels (i.e., macular pigment density, MPOD) were significantly related to performance on a variety of indices designed to assess processing speed, accuracy and completion ability (p≤0.05). These relations remained significant after adjusting for age, sex and ethnicity. Serum xanthophyll and fatty acid levels were not related to CF. MPOD, unlike serum xanthophylls, is a reflection of L and Z embedded into CNS tissue. The relation between MPOD and CF suggests that L and Z embedded in cortical tissue are capable of influencing cortical function. Additional research will be necessary to confirm these relations.Support:USDA#581950‐7‐07; DSM; AHAFMDR; NIHK23EY000409; N01AG62101; N01AG62103; N01AG62106; IRRF; RPB
Inhibition of Monkeypox virus replication by RNAi
Authors: Alkhalil Abdulnaser , Strand Sarah , Mucker Eric , Huggins John W , Jahrling Peter B , Ibrahim Sofi M 
Published: June 2021

Orthopoxviruses cause human diseases with various severities and outcome ranging from mild conditions to death in fulminating cases. Currently, vaccination is the only protective measure against infection with these viruses and no licensed antiviral drug therapy is available. We investigated the potential of RNA interference (RNAi) in inhibiting Monkeypox virus (MPV) replication. Based on genome‐wide expression study, we selected 12 viral genes for targeting by small interference RNA (siRNA). Forty‐eight siRNA constructs were developed and evaluated in vitro for their ability to inhibit viral replication. Two genes, each targeted with four different siRNA constructs in one pool, were detrimental to viral replication. Seven siRNA constructs from these two pools, targeting either an essential gene for viral replication (A6R) or an important gene in viral entry (E8L), inhibited viral replication in cell culture by 65–95% with no apparent cytotoxicity. Further analysis using wild‐type and recombinant MPV expressing green fluorescence protein identified the most potent construct (siA6‐a) that inhibited virus replication with IC50 less than 5nM. These results identify A6R as an essential gene in MPV replication, and validate RNAi applications in developing antivirals for MPV and other Orthopoxviruses.This work was supported by a grant from the DTRA, Project number 4.10022_07_RD_B.
Confirmatory factor analysis in nutrition and obesity research: Beyond dietary patterns
Authors: Lemacks Jennifer Lynn , Ilich Ernst Jasminka Z. 
Published: June 2021

Confirmatory factor analysis (CFA) is primarily used for determining population's dietary patterns in nutritional epidemiological studies. However, CFA also allows substitution of easily attained variables (BMI, girth circumferences) to represent a variable otherwise measured with expensive equipment by certified staff (e.g. DXA). Our objectives were to: 1. Provide example of a model for adiposity determination in 189 postmenopausal, overweight women utilizing CFA; 2. Determine the strength of association between latent construct “adiposity” and total body fat percent (%fat) measured by iDXA as reference. Mplus Editor (v5) was used for the analysis with following: waist/hip circumference, BMI, %IBW. The construct was compared with %fat (iDXA). Model fit indices include chi‐square test (χ2), root mean square error or approximation (RMSEA), comparative fit index (CFI), and Tucker‐Lewis index (TLI). RMSEA/SRMR≥0.8 and CFI/TLI ≤0.90 or 0.95 indicates poor fit. Model fit indices (χ2=13.48, df=7, RMSEA=.10, SRMR=.03, CFI=.99, TLI=.98) were optimal and the latent construct “adiposity” significantly correlated with %fat (r=.20, p=.05). Each of the body adiposity indicators alone has certain limitations but based on this analysis, they may be more informative when used in combination as a defined latent construct and therefore substitute for less easily obtained variables.USDA/CSREES/NRI#2004‐05287Grant Funding Source: USDA