bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling Vertebrate Development Dynamics in FrogXenopus laevisusing Micro-CT Imaging
Authors: Jakub Laznovsky , Michaela Kavkova , Alice Reis , Pavla Robovska-Havelkova , Jan Krivanek , Tomas Zikmund , Jozef Kaiser , Marcela Buchtova , Jakub Harnos 
Published: June 2024

AbstractBackgroundXenopus laevis, the African clawed frog, is a versatile vertebrate model organism employed across various biological disciplines, prominently in developmental biology to elucidate the intricate processes underpinning body plan reorganization during metamorphosis. Despite its widespread utility, a notable gap exists in the availability of comprehensive datasets encompassingXenopus’late developmental stages.FindingsIn the present study, we harnessed micro-computed tomography (micro-CT), a non-invasive 3D imaging technique utilizing X-rays to examine structures at a micrometer scale, to investigate the developmental dynamics and morphological changes of this crucial vertebrate model. Our approach involved generating high-resolution images and computed 3D models of developingXenopusspecimens, spanning from premetamorphosis tadpoles to fully mature adult frogs. This extensive dataset enhances our understanding of vertebrate development and is adaptable for various analyses. For instance, we conducted a thorough examination, analyzing body size, shape, and morphological features, with a specific emphasis on skeletogenesis, teeth, and organs like the brain at different stages. Our analysis yielded valuable insights into the morphological changes and structure dynamics in 3D space duringXenopus’development, some of which were not previously documented in such meticulous detail. This implies that our datasets effectively capture and thoroughly examineXenopusspecimens. Thus, these datasets hold the solid potential for additional morphological and morphometric analyses, including individual segmentation of both hard and soft tissue elements withinXenopus.ConclusionsOur repository of micro-CT scans represents a significant resource that can enhance our understanding ofXenopus’development and the associated morphological changes. The widespread utility of this amphibian species, coupled with the exceptional quality of our scans, which encompass a comprehensive series of developmental stages, opens up extensive opportunities for their broader research application. Moreover, these scans have the potential for use in virtual reality, 3D printing, and educational contexts, further expanding their value and impact.Graphical abstract & lay summary3D images of selected developmental stages ofX. laevisin a comparison (scale bar = 10 mm).Lay summaryX-ray tomography was used to examine the African clawed frog (Xenopus laevis). An extensive data set of specimens from tadpoles to adult frogs provides novel insights into the changes and developmental dynamics of selected structures, which opens avenues to an improved understanding of this crucial animal model.
UsingGalleria mellonellato study pathogen dissemination and anti-infective surface coatings
Authors: Maslova Evgenia , Staber Ciaram , McCarthy Ronan R 
Published: June 2024

AbstractHospital associated infections and localised hospital outbreaks are a major challenge for infection control teams (ICTs) in hospitals around the world. Advances in artificial intelligence and infection modelling have enabled ICT teams to better predict and trace infection spread. However, it is notoriously difficult to replicate bacterial dissemination or validate prediction models in a laboratory setting due to a lack of effectivein vivomodels. In this work, we sought to developGalleria mellonellaas a model organism to replicate the dissemination of pathogens in a hospital intensive care unit (ICU). By combining this model organism with 3D printed models of a real hospital ICU, we are able to demonstrate that larvae do disseminate the multidrug resistant pathogenAcinetobacter baumanniiwithin this ICU model and that it is possible to use this model to identify infection hotspots. Importantly, this model can also be used for intervention strategy testing as we also show that bacterial dissemination can be significantly mitigated by the introduction of antimicrobial wall surface coatings. This model provides a robust platform for the testing of antimicrobial surface coatings as well as the study of genetic determinants with a role in pathogen dissemination.
Gcn2 rescues reprogramming in the absence of Hog1/p38 signaling inC. neoformansduring thermal stress
Authors: Goich David , Bloom Amanda L. M. , Duffy Sean R. , Ventura Maritza N. , Panepinto John C. 
Published: June 2024

AbstractThe fungusCryptococcus neoformansis an opportunistic pathogen of people that reprograms its translatome to facilitate adaptation and virulence within the host. We studied the role of Hog1/p38 in reprogramming translation during thermal stress adaptation, and found that this pathway acts on translation via crosstalk with the Gcn2 pathway, a well-studied regulator of general translation control. Using a combination of molecular assays and phenotypic analysis, we show that increased output from the Gcn2 pathway in a Hog1 deletion mutant is associated with rescue of thermal stress adaptation at both molecular and phenotypic scales. We characterize known outputs of the Hog1 pathway during thermal stress as either Gcn2-dependent or Gcn2-independent, and demonstrate that Hog1 activation regulates the Gcn2 pathway even in the absence of thermal stress. Finally, we implicate this phenomenon in another Hog1-regulated process, morphogenesis, and recapitulate Hog1-Gcn2 crosstalk in the distantly related fungal pathogen,Candida albicans.Our results point to an important link between the stress response machinery and translation control, and clarify the etiology of phenotypes associated with Hog1 deletion. More broadly, this study highlights complex interplay between core conserved signal transduction pathways and the utility of molecular assays to better understand how these pathways are connected.ImportanceCryptococcus neoformansis an opportunistic pathogen of people that causes deadly cryptococcal meningitis, which is is responsible for an estimated 19% of AIDS-related mortality. When left untreated, cryptococcal meningitis is uniformly fatal, and in patients receiving the most effective antifungal regimens, mortality remains high. Thus, there is a critical need to identify additional targets that play a role in adaptation to the human host and virulence. This study explores the role of the stress response kinases Hog1 and Gcn2 in thermoadaptation, which is pre-requisite for virulence. Our results show that compensatory signaling occurs via the Gcn2 pathway when Hog1 is deleted, and that disruption of both pathways increases sensitivity to thermal stress. Importantly, our study highlights the insufficiency of using single gene deletion mutants to study gene function, since many phenotypes associated with Hog1 deletion were driven by Gcn2 signaling in this background, rather than loss of direct Hog1 activity.
Intestinal tissue response to Shiga toxin exposure
Authors: Hanson Kendal L. , Weiss Alison Ann 
Published: June 2024

AbstractShiga toxin (Stx) is produced by some pathogenic strains ofE. coli. To study the impact of Stx on the human intestine we utilized human intestinal organoids (HIOs) and human intestinal enteroids (HIEs) grown as human intestinal enteroid monolayers (HIEMs) in transwells. To establish optimal experimental conditions, HIEMs were grown with or without mesenchymal cells added to the basolateral wells to recapitulate the interactions between the intestinal epithelium and underlying mesenchyme. Monolayer barrier integrity was determined through transepithelial electrical resistance (TEER) readings. Apical saline was used on the apical surface since growth medium caused uneven development of the TEER. Medium used for epithelial cells contains added growth factors, while mesenchymal medium lacks these growth factors. We have shown that mesenchymal cells can maintain the epithelial monolayer in medium lacking growth factors suggesting they produce these factors. Furthermore, growth factors produced by mesenchymal cells need to buildup in the medium over time, since daily medium changes were not as effective as medium changes performed every three days. We have also shown that addition of growth factors is toxic to mesenchymal cells. Epithelial cells were more resistant to Stx2 than the mesenchymal cells, and mesenchymal cells contributed to epithelial cell death. Epithelial cells tolerated luminal exposure better than basolateral exposure. These studies demonstrate the importance of understanding tissue interactions in a disease state when using in vitro and in vitro models.ImportanceThese studies have cemented the need for complex cell culture models when studying host-pathogen interactions. Common animal models such as mice are resistant toE. coliO157:H7 infections and intestinal delivery of Stx2, while humans appear to be sensitive to both. It has been proposed that in humans, STEC-mediated intestinal damage destroys the intestinal barrier and allows basolateral access to Stx2. In mice, there is no epithelial damage, therefore they are resistant to epithelial delivery of Stx2, while remaining sensitive to Stx2 injection. Our studies show that like mice, the human epithelial layer is quite resistant to Stx2, and it is the sensitivity of the mesenchymal cells that kills the epithelial cells. We have shown that Stx2 is transported through the intact epithelium without causing damage to the resistant epithelial layer. Understanding tissue interactions during infections is therefore critical in determining the effects of pathogens on human tissues.
Microglia replacement effectively attenuates the disease progress of ALSP in the mouse model and human patient
Authors: Wu Jingying , Wang Yafei , Li Xiaoyu , Cai Yuanyuan , Ouyang Pei , He Yang , Zhang Mengyuan , Luan Xinghua , Jin Yuxiao , Liu Taohui , Li Yuxin , Huang Xiaojun , Mao Ying , Rao Yanxia , Cao Li , Peng Bo 
Published: June 2024

AbstractMicroglia play critical roles in the brain physiology and pathology. CSF1R is primarily expressed in microglia. The mono-allelicCSF1Rmutation causes adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a lethal neurological disease and no rational cure in clinical trials. There are no animal models mimicking human ALSP. In this study, we first developed mouse models based on human ALSP hotspot mutations. We then utilized microglia replacement by bone marrow transplantation (Mr BMT) to replace theCsf1r-deficient microglia in ALSP mice byCsf1r-normal donor cells. With pathogenic gene correction, Mr BMT efficiently attenuated the pathologies. Previously, an ALSP patient received traditional bone marrow transplantation (tBMT) due to a misdiagnosis of metachromatic leukodystrophy. The disease progress was halted for 15 years with unknown reasons. We demonstrated that tBMT in ALSP is equivalent to or close to Mr BMT, achieving efficient microglia replacement and therefore attenuating the ALSP progress in the mouse model. Next, we applied tBMT to replaceCSF1R-deficient microglia in human patients. Our clinical results show that after microglia replacement, the ALSP course is effectively halted. Together, microglia replacement corrects the pathogenic gene and thus halts the disease progress in the mouse model and human patients. This study strongly demonstrates clinical potentials of microglia replacement in neurological disease treatments.
Identifying factors that contribute to collision avoidance behaviours while walking in a natural environment
Authors: Nikmanesh Mohammadamin , Cinelli Michael E. , Marigold Daniel S. 
Published: June 2024

ABSTRACTBusy walking paths, like in a park, a sidewalk in a city centre, or a shopping mall, frequently necessitate collision avoidance behaviour. Lab-based research has shown how a variety of situation-specific factors (e.g., distraction, object/pedestrian proximity) and person-specific factors (e.g., pedestrian size, age), typically studied independently, affect avoidance behaviour. What happens in the real world is unclear. Thus, we filmed unscripted pedestrian walking behaviours on a busy ∼3.5 m urban path adjacent to the water. We leveraged deep learning algorithms to identify and extract walking trajectories of pedestrians and had unbiased raters characterize interaction details. Here we analyzed over 500 situations where two pedestrians approached each other from opposite ends (i.e., one-on-one pedestrian interactions). We found that smaller medial-lateral distance between approaching pedestrians and a lower number of surrounding pedestrians (i.e., smaller crowd size) predicted an increase in the likelihood of a subsequent path deviation. Furthermore, we found that whether a pedestrian looked distracted or held, pushed, or pulled something while walking predicted the medial-lateral distance between pedestrians at the time of crossing. Although pedestrians maintained a larger personal space boundary compared to lab settings, this is likely because of the outdoor path’s width. Overall, our results suggest that collision avoidance behaviours in lab and real-world environments share similarities and offer insights relevant to developing more accurate computational models for realistic pedestrian movement.
Culture-dependent identification of rare marine sediment bacteria from the Gulf of Mexico and Antarctica
Authors: Kennedy Sarah J. , Atkinson Celine Grace F. , Tubbs Tristan J. , Baker Bill J. , Shaw Lindsey N. 
Published: June 2024

AbstractLaboratory-viable cultivars of previously uncultured bacteria further taxonomic understanding. Despite many years of modern microbiological investigations, the vast majority of bacterial taxonomy remains uncharacterized. While many attempts have been made to decrease this knowledge gap, culture-based approaches parse away at the unknown and are critical for improvement of both culturing techniques and computational prediction efficacy. To this end of providing culture-based approaches, we present a multi-faceted approach to recovering marine environmental bacteria. We employ combinations of nutritional availability, inoculation techniques, and incubation parameters in our recovery of marine sediment-associated bacteria from the Gulf of Mexico and Antarctica. The recovered biodiversity spans several taxa, with 16S-ITS-23S rRNA gene-based identification of multiple isolates belonging to rarer genera increasingly undergoing phylogenetic rearrangements. Our modifications to traditional culturing techniques have not only recovered rarer taxa, but also resulted in the recovery of biotechnologically promising bacteria. Together, we propose our stepwise combinations of recovery parameters as a viable approach to decreasing the bacterial knowledge gap.
New Insights into Neuromuscular Contracture Reveals Myotendinous-SMAD4 Signaling Underlies Contracture Formation
Authors: Arvind Varun , Shyu Peter Timothy , Hyman Joshua E. , Huang Alice H. 
Published: June 2024

ABSTRACTNeuromuscular contractures (NC) are a prevalent cause of joint deformity in children suffering from neuromuscular disorders or nerve damage, leading to persistent disability. The role of tendon in the development of NC remains poorly understood, with current treatments predominantly targeting muscle. Here, we establish a surgical model of NC in the hindlimb that recapitulates functional deformity and transcriptomic changes observed in human disease. Our findings indicate that in NC, tendons dramatically elongate, undergoing changes in matrix and structural composition that reduce tensile stiffness. Contrary to expectations, we find that tendon elongation was principally driven by increased myotendon infiltration into muscle which restricted muscle elongation contributing to NC. Using lineage tracing, we show that myotendon elongation was due to increased infiltration of intrinsically derived tenocytes. Transcriptional profiling revealed BMP signaling as a key factor in myotendon elongation, corroborated by elevated myotendinous Smad4 activity in both our mouse model and in human NC tissues. Crucially, administration of a small molecule inhibitor of BMP-mediated Smad4 signaling not only restored joint mobility but also prevented myotendon elongation. These insights establish of a clinically relevant mouse model of NC and unveil a novel role for myotendon elongation in NC progression. Excitingly, our results suggest that targeting myotendon signaling could represent a new direction for tendon-focused therapies in NC management.
An algicidal bacterium shapes the microbiome during outdoor diatom cultivation collapse
Authors: Gilbert Naomi E. , Kimbrel Jeffery A. , Samo Ty J. , Siccardi Anthony J. , Stuart Rhona K. , Mayali Xavier 
Published: June 2024

AbstractBiogeochemistry and productivity of algae-dominated environments is fundamentally influenced by the diversity and activity of bacteria. Namely, algicidal bacteria that prey on algal hosts can control elemental cycling and host populations within outdoor algal ponds used for biofuel production. In this study, we describe the genomic and proteomic signatures of a putative algicidal bacterium,Kordiasp. (familyFlavobacteriaceae), that bloomed during a population-wide crash of the biofuel diatom,Phaeodactylum tricornutum. ThisKordiasp. bloom occurred after 29 days of cultivation in outdoor algal raceway ponds inoculated withP. tricornutum, but not in parallel ponds inoculated withMicrochloropsis salina. Several signatures of antagonism expressed byKordiaduring diatom demise highlights previously unexplored mechanisms that may aid in algicidal activity or bacterial competition, including the type VI secretion system and hydrogen peroxide production. Analysis of accompanying downstream microbiota (primarily of theRhodobacteraceaefamily) provides evidence that cross-feeding is important in supporting microbial diversity during algal demise. Specifically,in situand laboratory data suggest thatKordiaacts as a primary degrader of biopolymers during algal demise, and co-occurringRhodobacteraceaeexploit degradation molecules or scavenge metabolic byproducts for carbon. Further, targeted analysis of 30Rhodobacteraceaemetagenome assembled genomes suggest algal pondRhodobacteraceaecommonly harbor pathways for carbon monoxide oxidation, a potential strategy to persist under competition. Collectively, these observations further constrain the role of algicidal bacteria in the aquatic ecosystem.
Exploring metabolic changes in gout – Insights from a genetic study
Authors: Salo Ville , Kettunen Johannes ,   FinnGen,   Estonian Biobank Research Team, Sliz Eeva 
Published: June 2024

AbstractGout is the most common inflammatory joint disease caused by the crystallization of urate inside the joints. Patients with gout typically have abnormal blood lipid and sugar levels, which are associated with cardiovascular diseases. However, the relationship between gout and metabolic changes is unclear. Our goal was two-fold: to identify new gout risk factors using genome-wide association analysis and subsequently to investigate the effects of the identified risk alleles on metabolic measures in the bloodstream. We performed a genome-wide meta-analysis for gout in the FinnGen project, the Estonian Biobank, and the UK Biobank, encompassing a total of 992,583 individuals, including 17,972 gout cases. Given that gout is commonly recognized as a disease affecting the elderly, and males specifically, we further explored age- and sex-stratified genetic associations in FinnGen (10,885 cases and 366,392 controls). Finally, we determined the metabolomic consequences of the gout risk-increasing alleles using data from a large metabolomics GWAS. In the meta-analysis, we observed 32 genome-wide significant (P<5×10−8) loci, one of which was novel. In the age- and sex-stratified analyses, we additionally identified one novel gout-associated locus in the male subgroup. The metabolomic findings suggested that the majority of the gout risk alleles primarily affected urate concentration in the bloodstream but not the concentrations of lipids and other metabolites. Therefore, it appears that the associations between gout and metabolic factors at the population level are likely explained by shared lifestyle risk factors. In conclusion, our study sheds new light on the genetic architecture of gout and adds to the growing body of evidence supporting the role of urate, but not other metabolic measures, including lipoprotein lipids and glucose, as a key risk factor for developing gout.
Blockchain based clinical trial management system: A scoping review and conceptual framework
Authors: Arjun M. C. , Ahamed Ashikh , Kurpad Anura V. , Thomas Tinku 
Published: June 2024

AbstractObjectiveThe primary objective of the study was to map the real-world evidence of using Blockchain technology in clinical trial management systems and to create a novel conceptual framework for a Blockchain based digital ecosystem. As a first step towards validation of this conceptual framework, we aimed to create a blockchain simulation in Python programming language.MethodsWe did a scoping review of research articles which demonstrated a proof-of-concept or real-world application of Blockchain technology in clinical trial management. We searched in the PubMed, Web of Science, and IEEE Xplore to retrieve original articles published in English till April 2023. A novel conceptual framework was developed for a Blockchain based digital ecosystem with all the stakeholders involved in the conduct of clinical trial. We coded a simulation of clinical trial specific blockchain in Python using Django framework and the codes are made publicly available in GitHub.ResultsWe retrieved 960 abstracts and included 21 full text articles in the review. Private blockchains like Hyperledger fabric and Ethereum are the most popular choice of platform. Smart contracts act as a key functionality in the Blockchain system to control specific activities. Clinical trial data was mostly stored outside the Blockchain, but Interplanetary File System is a popular choice for decentralized storage of data.ConclusionsThe scoping review, conceptual framework and the open-source Python codes would act as a guiding map for future research and product development in Blockchain based clinical trial management system and advancement in clinical research informatics.
How does the
X(3872)
show up in
e+e−
collisions: Dip versus peak
Authors: Baru Vadim , Guo Feng-Kun , Hanhart Christoph , Nefediev Alexey 
Published: June 2024

We demonstrate that the dip observed near the total energy of 3872 MeV in the recent cross section data from the BESIII Collaboration for e+e−→J/ψπ+π− admits a natural explanation as a coupled-channel effect: it is a consequence of unitarity and a strong S-wave DD¯* attraction that generates the state X(3872). We anticipate the appearance of a similar dip in the e+e−→J/ψπ+π−π0 final state near the D*D¯* threshold driven by the same general mechanism, then to be interpreted as a signature of the predicted spin-2 partner of the X(3872).

Published by the American Physical Society
2024