bluuebunny/crossref_metadata_2025_split huggingface dataset:
The dentary of hadrosauroid dinosaurs: evolution through heterochrony
Authors: Söderblom D. Fredrik K. , Blanco Alejandro , Prieto‐Márquez Albert , Campione Nicolás E. 
Published: October 2023

AbstractThe near‐global distribution of hadrosaurid dinosaurs during the Cretaceous has been attributed to mastication, a behaviour commonly recognized as a mammalian adaptation. Its occurrence in a non‐mammalian lineage should be accompanied by the evolution of several morphological modifications associated with food acquisition and processing. This study investigated morphological variation in the dentary, a major element of the hadrosauroid lower jaw. Eighty‐four hadrosauroid dentaries were subjected to geometric morphometric and statistical analyses to investigate their taxonomic, ontogenetic, and individual variation. Results suggest increased food acquisition and processing efficiency in saurolophids through a complex pattern of evolutionary and growth‐related changes. The edentulous region grew longer relative to dentary length, allowing for food acquisition specialization anteriorly and processing posteriorly, and became ventrally directed, possibly associated with foraging low‐growing vegetation, especially in younger individuals. The saurolophid coronoid process became anteriorly directed and relatively more elongate, with an expanded apex, increasing moment arm length, with muscles pulling the jaw more posteriorly, increasing mechanical advantage. During growth, all hadrosauroids underwent anteroposterior dental battery elongation by the addition of teeth, and edentulous region ventralization decreased. The dental battery became deeper in saurolophids by increasing the number of teeth per tooth family. The increased coronoid process anterior inclination and relative edentulous region elongation in saurolophids are hypothesized to have evolved through hypermorphosis and/or acceleration, peramorphic heterochronic processes; the development of an anteroposteriorly shorter but dorsoventrally taller saurolophid dentary, is probably due to post‐displacement in dental battery elongation and edentulous region decreased ventral orientation, a paedomorphic heterochronic process.
Soybean‐Phakopsora pachyrhizi interactions: towards the development of next‐generation disease‐resistant plants
Authors: Chicowski Aline Sartor , Bredow Melissa , Utiyama Alice Satiko , Marcelino‐Guimarães Francismar Corrêa , Whitham Steven A. 
Published: October 2023

SummarySoybean rust (SBR), caused by the obligate biotrophic fungus Phakopsora pachyrhizi, is a devastating foliar disease threatening soybean production. To date, no commercial cultivars conferring durable resistance to SBR are available. The development of long‐lasting SBR resistance has been hindered by the lack of understanding of this complex pathosystem, encompassing challenges posed by intricate genetic structures in both the host and pathogen, leading to a gap in the knowledge of gene‐for‐gene interactions between soybean and P. pachyrhizi. In this review, we focus on recent advancements and emerging technologies that can be used to improve our understanding of the P. pachyrhizi‐soybean molecular interactions. We further explore approaches used to combat SBR, including conventional breeding, transgenic approaches and RNA interference, and how advances in our understanding of plant immune networks, the availability of new molecular tools, and the recent sequencing of the P. pachyrhizi genome could be used to aid in the development of better genetic resistance against SBR. Lastly, we discuss the research gaps of this pathosystem and how new technologies can be used to shed light on these questions and to develop durable next‐generation SBR‐resistant soybean plants.
Signatures of dysbiosis in fish microbiomes in the context of aquaculture
Authors: Xavier Raquel , Severino Ricardo , Silva Sofia M. 
Published: October 2023

AbstractFish microbiome plays an important role in maintaining host homeostasis, with many bacterial functions directly linked to host fitness. Fish microbiome research is advancing fast, especially in the context of aquaculture where several stressors are known to disrupt stability of host‐associated bacteria, prompting dysbiosis. Therefore, understanding the signatures of dysbiosis in different fish mucosae and their association with such stressors is fundamental to set up efficient health‐monitoring strategies, as well as sound and objective working hypothesis for future research. Herein, we reviewed studies that employed culture‐independent approaches to assess the effects of disease, chemotherapeutics and water quality changes on several diversity metrics of gut, skin and gill microbiomes. We conclude that increases in abundance of potential pathogens and changes to bacterial community structure are reliable indicators of dysbiosis in fish. The gut microbiome emerged as being highly susceptible to salinity changes and chemotherapeutics, whereas external microbiota seems to be more susceptible to dysbiosis caused by disease and temperature changes. Our analysis showed that treatments with tetracyclines and florfenicol are more likely to elicit severe dysbiosis compared to quinolones and disinfectants that cause lesser disturbance to fish microbiome. Bacterial diseases also frequently elicit severe dysbiosis (enteritis in particular), whereas parasitic diseases are far less deleterious. Regarding impacts on water quality, only changes to salinity and temperature are reasonably studied. Recent developments in metagenomics, that include a fast turn‐around time of results, can be used to detect changes to fish homeostasis during critical periods of fish production, assisting aquaculture management.
‘De voluptate aurium’: The sounds of heaven in a 1501 sensory treatise on the afterlife
Authors: Ștefănescu Laura 
Published: October 2023

AbstractIn his De gloria et gaudiis beatorum, printed in 1501, the clergyman Zaccaria Lilio explores a popular topic in the religious life of Renaissance Italy: what is heaven like and what kind of experience awaits the blessed there? And his answer represents a snapshot of a characteristic manner in which heaven was imagined in the period, both in written and visual form, one strongly focused on a sensory understanding of the afterlife and in which music played an important part. By identifying the sources of Lillio's interpretation of the sense of hearing in the afterlife, a network of clergymen interested in heavenly sensory delights is revealed, initiated by an Italian curiosity for a fourteenth‐century text by a follower of Meister Eckart. This article aims not only to bring to the attention of scholars Lilio's neglected sensory treatise, but also to provide an in‐depth analysis of the intricate connections between Italian authors of sensory treatises from the fifteenth century. The implications of this textual tradition disseminated through preaching are of great importance to the development of the image of heaven and its music in Renaissance Italy, for which the sensory perspective was of crucial importance.
Genetic basis of the historical iron‐accumulating dgl and brz mutants in pea
Authors: Harrington Sophie A. , Franceschetti Marina , Balk Janneke 
Published: October 2023

SUMMARYThe Pisum sativum (pea) mutants degenerate leaves (dgl) and bronze (brz) accumulate large amounts of iron in leaves. First described several decades ago, the two mutants have provided important insights into iron homeostasis in plants but the underlying mutations have remained unknown. Using exome sequencing we identified an in‐frame deletion associated with dgl in a BRUTUS homolog. The deletion is absent from wild type and the original parent line. BRUTUS belongs to a small family of E3 ubiquitin ligases acting as negative regulators of iron uptake in plants. The brz mutation was previously mapped to chromosome 4, and superimposing this region to the pea genome sequence uncovered a mutation in OPT3, encoding an oligopeptide transporter with a plant‐specific role in metal transport. The causal nature of the mutations was confirmed by additional genetic analyses. Identification of the mutated genes rationalizes many of the previously described phenotypes and provides new insights into shoot‐to‐root signaling of iron deficiency. Furthermore, the non‐lethal mutations in these essential genes suggest new strategies for biofortification of crops with iron.
Mechanical Response of Fisherman’s Knots During Tightening
Authors: Tong Dezhong , Ibrahim Khalil Md , Justin Silva Matthew , Wang Guanjin , Khoda Bashir , Khalid Jawed Mohammad 
Published: October 2023

Abstract
The fisherman’s knot, renowned for its strength and reliability, finds applications in engineering and medicine. However, a comprehensive understanding of its mechanics remains limited in scientific literature. In this paper, we present a systematic study of the tightening behavior of the fisherman’s knot through a combined approach of tabletop experiments and discrete elastic rods simulations. Our experimental setup involves gradually applying tension to the two ends of the fisherman’s knot until it fractures. We observed a correlation between the knot’s material properties and its behavior during tightening, leading up to fracture. The tightening process of the fisherman’s knot exhibits distinct “sliding” or “stretching” motions, influenced by factors such as friction and elastic stiffness. Furthermore, the failure modes of the knot (material fracture and topological failure) are determined by an interplay between elastic stiffness, friction, and initial conditions. This study sheds light on the underlying mechanics of the fisherman’s knot and provides insight into its behavior during the tightening process, contributing to the broader understanding of the mechanics of knots in practical applications.
Population pharmacokinetic model of cefepime for critically ill adults: a comparative assessment of eGFR equations
Authors: Barreto Erin F. , Chang Jack , Rule Andrew D. , Mara Kristin C. , Meade Laurie A. , Paul Johar , Jannetto Paul J. , Athreya Arjun P. , Scheetz Marc H. ,   for the BLOOM Study Group
Published: October 2023

ABSTRACT

Cefepime exhibits highly variable pharmacokinetics in critically ill patients. The purpose of this study was to develop and qualify a population pharmacokinetic model for use in the critically ill and investigate the impact of various estimated glomerular filtration rate (eGFR) equations using creatinine, cystatin C, or both on model parameters. This was a prospective study of critically ill adults hospitalized at an academic medical center treated with intravenous cefepime. Individuals with acute kidney injury or on kidney replacement therapy or extracorporeal membrane oxygenation were excluded. A nonlinear mixed-effects population pharmacokinetic model was developed using data collected from 2018 to 2022. The 120 included individuals contributed 379 serum samples for analysis. A two-compartment pharmacokinetic model with first-order elimination best described the data. The population mean parameters (standard error) in the final model were 7.84 (0.24) L/h for CL1 and 15.6 (1.45) L for V1. Q was fixed at 7.09 L/h and V2 was fixed at 10.6 L, due to low observed interindividual variation in these parameters. The final model included weight as a covariate for volume of distribution and the eGFR
cr-cysC
(mL/min) as a predictor of drug clearance. In summary, a population pharmacokinetic model for cefepime was created for critically ill adults. The study demonstrated the importance of cystatin C to prediction of cefepime clearance. Cefepime dosing models which use an eGFR equation inclusive of cystatin C are likely to exhibit improved accuracy and precision compared to dosing models which incorporate an eGFR equation with only creatinine.
Co-administration of chicken IL-2 alleviates clinical signs and replication of the ILTV chicken embryo origin vaccine by pre-activating natural killer cells and cytotoxic T lymphocytes
Authors: Hao Xiaoli , Li Jiaqi , Wang Jiongjiong , Zhou Zhou , Yuan Xinjie , Pan Shan , Zhu Jie , Zhang Fan , Yin Shi , Yang Yi , Hu Shunlin , Shang Shaobin 
Published: October 2023

ABSTRACT
The chicken embryo origin (CEO) vaccine of infectious laryngotracheitis virus (ILTV) confers the best protection against ILTV but causes adverse reactions due to its swift replication, thus limiting its use in poultry flocks. Seeking a strategy to alleviate the adverse reactions of the vaccine is most desirable for its safe use. Here, we observed that co-administration of chIL-2 significantly alleviated the clinical signs induced by the CEO vaccine in chickens. To address the underlying mechanism, we examined the cellular immune response of chickens treated with or without chIL-2 by multicolor flow cytometry and evaluated the impact of chIL-2 on the protective efficacy and replication of the CEO vaccine after the challenge. The results showed that co-administration of chIL-2 was associated with a decrease in the clinical signs and CEO viral load in tissues and induced a rapid and significant expansion of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) as well as upregulated expression of cytotoxic and T-cell-related cytokines at the early stage, especially in trachea and conjunctiva. However, chIL-2 treatment has no negative effect on the recall responses of NK cells, γδ T cells, and CTLs associated with the protective efficacy of the CEO vaccine after the ILTV challenge. Collectively, our results suggest that co-administration of chIL-2 with the CEO vaccine ameliorated the replication of the CEO vaccine by enhancing chicken NK cell and CTLs responses without affecting its protective efficacy.

IMPORTANCE
Chickens immunized with the infectious laryngotracheitis chicken embryo origin (CEO) vaccine (Medivac, PT Medion Farma Jaya) experience adverse reactions, hindering its safety and effective use in poultry flocks. To improve the effect of the vaccine, we sought to find a strategy to alleviate the respiratory reactions associated with the vaccine. Here, we confirmed that co-administering the CEO vaccine with chIL-2 by oral delivery led to significant alleviation of the vaccine reactions in chickens after immunization. Furthermore, we found that the co-administration of chIL-2 with the CEO vaccine reduced the clinical signs of the CEO vaccine while enhancing natural killer cells and cytotoxic T lymphocyte response to decrease viral loads in their tissues, particularly in the trachea and conjunctiva. Importantly, we demonstrated that the chIL-2 treatment can ameliorate the replication of the CEO vaccine without compromising its effectiveness. This study provides new insights into further applications of chIL-2 and a promising strategy for alleviating the adverse reaction of vaccines.
PGAM5 degrades PDCoV N protein and activates type I interferon to antagonize viral replication
Authors: Yang Xinyu , Kong Ning , Qin Wenzhen , Zhai Xueying , Song Yiyi , Tong Wu , Li Liwei , Liu Changlong , Zheng Hao , Yu Hai , Zhang Wen , Tong Guangzhi , Shan Tongling 
Published: October 2023

ABSTRACT
In recent years, porcine deltacoronavirus (PDCoV) has become a new intestinal coronavirus in pigs, rapidly spreading across multiple countries and causing significant financial losses in the global pig industry. Currently, no effective commercial vaccine is available to prevent this virus’ spread. Thus, it becomes crucial to investigate the interaction between the virus and its host to acquire valuable insights into the underlying mechanisms of viral replication and develop innovative strategies for preventing and controlling PDCoV. This study specifically focuses on exploring the regulatory effects of PGAM5, a mitochondrial protein, during viral proliferation. Our findings suggest that PDCoV infection hinders the expression of PGAM5 in LLC-PK1 cells. Additionally, it was also found that PGAM5 facilitates the degradation of the PDCoV N protein via the interaction with it, thereby inhibiting viral proliferation. Notably, the degradation of the PDCoV N protein by PGAM5 is mediated through its interaction with the cargo receptor P62 and the E3 ubiquitination ligase STUB1 during the protein degradation process. Furthermore, our results demonstrate that PGAM5 enhances the phosphorylation of IRF7, resulting in increased expression of type I interferon through its interaction with MyD88 and TRAF3, ultimately inhibiting PDCoV replication. Collectively, these findings elucidate the antiviral mechanism of PGAM5, which involves the degradation of the PDCoV N protein and activation of type I interferon to counteract viral replication. The obtained results emphasize the potential of PGAM5 as the novel target for preventing and treating PDCoV.

IMPORTANCE
As a member of the δ-coronavirus family, porcine deltacoronavirus (PDCoV) is a vital reason for diarrhea in piglets, which can contribute to high morbidity and mortality rates. Initially identified in Hong Kong in 2012, the virus has rapidly spread worldwide. During PDCoV infection, the virus employs evasion mechanisms to evade host surveillance, while the host mounts corresponding responses to impede viral replication. Our research has revealed that PDCoV infection down-regulates the expression of PGAM5 to promote virus replication. In contrast, PGAM5 degrades PDCoV N through autophagy by interacting with the cargo receptor P62 and the E3 ubiquitination ligase STUB1. Additionally, PGAM5 interacts with MyD88 and TRAF3 to activate the IFN signal pathway, resulting in the inhibition of viral replication.
Regulation of the WNT-CTNNB1 signaling pathway by severe fever with thrombocytopenia syndrome virus in a cap-snatching manner
Authors: Jiang Xia-Ming , Xin Qi-Lin , Liu Kai , Peng Xue-Fang , Han Shuo , Zhang Ling-Yu , Liu Wei , Xiao Geng-Fu , Li Hao , Zhang Lei-Ke 
Published: October 2023

ABSTRACT

The segmented negative-strand RNA viruses (sNSVs) include highly pathogenic human and animal viruses such as Lassa virus (LASV), severe fever with thrombocytopenia syndrome virus (SFTSV), and influenza A virus (IAV). One of the conserved mechanisms at the stage of genome transcription of sNSVs is the cap-snatching process, providing druggable targets for the development of antivirals. SFTSV is an emerging tick-borne sNSV that causes severe hemorrhagic fever with a high fatality rate of 12%–50%. Here, we determined the correlation between death outcome and downregulation of the WNT-CTNNB1 signaling pathway through transcriptomic analysis of blood samples collected from SFTS patients. We further demonstrated that SFTSV affected this pathway by downregulating the mRNA levels of a series of pathway-related genes, including
CTNNB1
. Loss-of-function mutations or inhibitors targeting SFTSV cap-snatching activity effectively alleviated the inhibition of the WNT-CTNNB1 signaling pathway. Exogenous activation of the WNT-CTNNB1 signaling pathway enhanced SFTSV replication, while inhibition of this pathway reduced SFTSV replication. Treatment with a WNT-CTNNB1 signaling pathway inhibitor attenuated viral replication and decreased fatality in mice. Notably, downregulation of the WNT-CTNNB1 signaling pathway was also observed for other sNSVs, including LASV and IAV. These results suggested that RNAs related to the WNT-CTNNB1 signaling pathway might be utilized as a primer “pool” in a cap-snatching manner for viral transcription, which provides effective targets for the development of broad-spectrum antivirals against sNSVs.

IMPORTANCE

One of the conserved mechanisms at the stage of genome transcription of segmented negative-strand RNA viruses (sNSVs) is the cap-snatching process, which is vital for sNSVs transcription and provides drugable targets for the development of antivirals. However, the specificity of RNAs snatched by sNSV is still unclear. By transcriptomics analysis of whole blood samples from SFTS patients, we found WNT-CTNNB1 signaling pathway was regulated according to the course of the disease. We then demonstrated that L protein of severe fever with thrombocytopenia syndrome virus (SFTSV) could interact with mRNAs of WNT-CTNNB1 signaling pathway-related gene, thus affecting WNT-CTNNB1 signaling pathway through its cap-snatching activity. Activation of WNT-CTNNB1 signaling pathway enhanced SFTSV replication, while inhibition of this pathway decreased SFTSV replication
in vitro
and
in vivo
. These findings suggest that WNT-associated genes may be the substrate for SFTSV “cap-snatching”, and indicate a conserved sNSVs replication mechanism involving WNT-CTNNB1 signaling.
A novel RofA-family transcriptional regulator, GadR, controls the development of acid resistance in
Listeria monocytogenes
Authors: Wu Jialun , McAuliffe Olivia , O'Byrne Conor P. 
Published: October 2023

ABSTRACT

Stomach acid provides a significant innate barrier to the entry of the food-borne pathogen
Listeria monocytogenes
into the human gastrointestinal tract. A key determinant of acid resistance in this bacterium is the conserved glutamate decarboxylase system, GadD2 (encoded by the
gadT2D2
operon), which helps to maintain the intracellular pH during exposure to gastric acid. In this study, we identified a premature stop codon in a gene located immediately downstream of the
gadT2D2
operon that was highly linked to an acid-sensitive phenotype. When this open reading frame was restored through homologous recombination, an acid-resistant phenotype was restored. Through a series of genetic, transcriptomic, and survival experiments, we established that this gene, which we designated
gadR
, encodes a transcriptional regulator of the
gadT2D2
operon. GadR belongs to the RofA family of regulators, primarily found in streptococci, where they are involved in regulating virulence. The data further showed that
gadR
plays a critical role in the development of acid resistance in response to mild acid exposure, a response that is known as the adaptive acid tolerance response (ATR). A deletion analysis of the
gadT2D2
promoter region identified two 18-bp palindromic sequences that are required for the GadR-mediated induction of
gadT2D2
, suggesting that they act as binding sites for GadR. Overall, this study uncovers a new RofA-like regulator of acid resistance in
L. monocytogenes
, which plays a significant role in both growth phase-dependent acid resistance and ATR and accounts for previously observed strain-to-strain differences in survival at low pH.

IMPORTANCE

The ability to survive the acidic conditions found in the stomach is crucial for the food-borne pathogen
Listeria monocytogenes
to gain access to the mammalian gastrointestinal tract. Little is currently known about how acid resistance is regulated in this pathogen and why this trait is highly variable between strains. Here, we used comparative genomics to identify a novel RofA-family transcriptional regulator, GadR, that controls the development of acid resistance. The RofA family of regulators was previously found only in a small group of bacterial pathogens, including streptococci, where they regulate virulence properties. We show that
gadR
encodes the dominant regulator of acid resistance in
L. monocytogenes
and that its sequence variability accounts for previously observed differences between strains in this trait. Together, these findings significantly advance our understanding of how this important pathogen copes with acid stress and suggest a potential molecular target to aid its control in the food chain.