bluuebunny/crossref_metadata_2025_split huggingface dataset:
Social dominance status and social stability in spiny mice (Acomys cahirinus) and its relation to ear-hole regeneration and glucocorticoids
Authors: Varholick Justin A. , Godinez Gizelle , Mobin Sarim , Jenkins Ashley , Romeo Russell D. , Corll Jacob , Barbazuk W. Brad , Maden Malcolm 
Published: September 2022

AbstractSpiny mice (Acomys cahirinus) are an emerging animal model in studies measuring tissue regeneration, but decades of research on social dominance in other animals indicates the relationships animals form in their home-cage may affect phenotypic plasticity in tissue regeneration and glucocorticoids. Studies in baboons and mice, for example, indicate that subordinate ranked animals heal wounds slower than their dominant group-mates, and have increased levels of basal glucocorticoids. Recent studies in tissue regeneration with salamanders and zebrafish indicate that increased glucocorticoids can delay tissue regeneration, but whether this effect extends toAcomysis unknown, especially regarding their social dominance relationships. Here we report that most adultAcomyshad a social dominance status, but many groups had unclear social stability, with more frequent huddling than fighting during their active cycle. We also found no sex differences in social dominance behavior, and thatAcomysmore frequently fled than froze when chased or approached. After a 4mm ear-pinna biopsy, we found that social stability significantly accounted for variability in time to close the ear-hole but adding age to the statistical model removed the effect of social stability. When investigating glucocorticoid blood levels, there were no significant effects of social dominance status or social stability. A transcriptional enhancer for StAR, Nr5a1 had a significant effect for the interaction of social dominance status and social stability. This effect, however, was not reflected in StAR and unclear groups mostly had unclear social statuses, so this effect should be considered with caution. This is the first study to investigate home-cage social dominance behaviors inAcomyssince the 1970s or measure any associations with their ability to regenerate tissue. This provides a platform for further work on their social dominance and glucocorticoids and highlights the need to consider the role of aging in their ability to regenerate tissue.
Chronic stress exposure alters the gut barrier: sex-specific effects on microbiota and jejunum tight junctions
Authors: Doney Ellen , Dion-Albert Laurence , Coulombe-Rozon Francois , Osborne Natasha , Bernatchez Renaud , Paton Sam E.J. , Kaufmann Fernanda Neutzling , Agomma Roseline Olory , Solano José L. , Gaumond Raphael , Dudek Katarzyna A. , Szyszkowicz Joanna Kasia ,   Signature Consortium, Lebel Manon , Doyen Alain , Durand Audrey , Lavoie-Cardinal Flavie , Audet Marie-Claude , Menard Caroline 
Published: September 2022

AbstractMajor depressive disorder (MDD) is the leading cause of disability worldwide. However, 30-50% of patients are unresponsive to commonly prescribed antidepressants, highlighting untapped causal biological mechanisms. Dysfunction in the microbiota-gut-brain axis, the bidirectional communications between the central nervous system and gastrointestinal tract that are modulated by gut microorganisms, has been implicated in MDD pathogenesis. Exposure to chronic stress disrupts blood-brain barrier integrity, still, little is known about intestinal barrier function in these conditions particularly for the small intestine where most food and drug absorption takes place. Thus, here we investigate how chronic social or variable stress, two mouse models of depression, impact the jejunum (JEJ) intestinal barrier in males and females. Mice were subjected to stress paradigms followed by analysis of gene expression profiles of intestinal barrier-related targets, fecal microbial composition, and blood-based markers. Altered microbial populations as well as changes in gene expression of JEJ tight junctions were observed depending on the type and duration of stress, with sex-specific effects. We took advantage of machine learning to characterize in detail morphological tight junction properties identifying a cluster of ruffled junctions in stressed animals. Junctional ruffling is associated with inflammation, so we evaluated if LPS injection recapitulates stress-induced changes in the JEJ and observed profound sex differences. Finally, LPS-binding protein (LBP), a marker of gut barrier leakiness, was associated with stress vulnerability in mice and translational value was confirmed on blood samples from women with MDD. Our results provide evidence that chronic stress disrupts intestinal barrier homeostasis in conjunction with the manifestation of depressive-like behaviors in a sex-specific manner in mice and possibly, human depression.
Mevalonate metabolites contribute to granulocyte chemotaxis and mortality in murine endotoxemia
Authors: Hussain Jamal , Ousley Carey G. , Krauklis Steven A. , Dray Evan L. , Drnevich Jenny , Justyna Katarzyna , Distefano Mark D. , McKim Daniel B. 
Published: September 2022

AbstractStatins appear to dramatically increase sepsis survival but only when treatment is initiated prior to hospitalization. This implies that statins exhibit a delayed-onset pro-survival benefit in septic patients that results in clinical futility of statin-therapy for patients already diagnosed with sepsis. Identification of mechanisms that contribute to increased sepsis-survival following statin-pretreatment may reveal novel therapeutic targets that do not suffer similar delayed onset benefits. Statins are used to treat hypercholesterolemia and function by inhibiting the production of the rate-limiting metabolite mevalonate. This indirectly inhibits the de novo synthesis of not only cholesterol but also isoprenoids that are involved in prenylation, the post-translational lipid modification of proteins. Mirroring clinical observations, chronic but not acute treatment with simvastatin significantly increased survival in a murine endotoxemia model. This was associated with reduced systemic granulocyte chemotaxis that occurred in a cell-intrinsic manner. In vitro modeling showed that simvastatin abolished chemoattractant responses and that this could be reversed by restoring geranylgeranyl pyrophosphate (GGPP) but not farnesyl pyrophosphate (FPP) nor cholesterol. Treatment with prenyltransferase inhibitors showed that chemoattractant responses were dependent on geranylgeranylation. Proteomic analysis of C15AlkOPP-prenylated proteins identified geranylgeranylated proteins involved in chemoattractant responses, including RHOA, RAC1, CDC42, and GNG2. Given the kinetic problems with initiating statin treatment after sepsis onset, prenyltransferases and geranylgeranylated proteins, such as RAC1 and GNG2, are promising interventional candidates for sepsis and critical inflammatory illness.
Urbanisation impacts plumage colouration in a songbird across Europe: evidence from a correlational, experimental, and meta-analytical approach
Authors: Salmón Pablo , López-Idiáquez David , Capilla-Lasheras Pablo , Pérez-Tris Javier , Isaksson Caroline , Watson Hannah 
Published: September 2022

AbstractUrbanisation is increasing at a phenomenal rate across the globe, transforming landscapes, presenting organisms with novel challenges, shaping phenotypic traits, and even impacting fitness. Among colour traits, urban individuals are widely claimed to have duller tones in carotenoid-based traits, the so-called “urban dullness” phenomenon. However, at the intra-specific level, this generalisation is surprisingly inconsistent and often based on examples from single urban/non-urban population pairs or a limited geographic area. Here, combining correlational, experimental, and meta-analytical results from a common songbird, the great tit (Parus major), we investigated carotenoid-based plumage coloration in urban and forest populations across Europe. We find that, as predicted, urban individuals are paler than forest individuals. Interestingly, we also find large population-specific differences in the magnitude of the urban-forest contrast in plumage colouration. Moreover, our meta-analysis indicates a non-significant effect of environmental pollution on carotenoid-based plumage for the species, suggesting that the observed differences across urban populations are not only driven by pollution. Finally, using one region as an example (Malmö, Sweden), we reveal population-specific processes behind plumage colouration differences, which are likely the result of variation in the spatial and temporal distribution of carotenoid-rich resources in anthropogenic environments. This is the first study to quantify the consistency of an oft-cited textbook example of the impact of urbanisation on wildlife; our results provide the most convincing evidence to date of the “urban dullness” phenomenon, but also highlight that the magnitude of the phenomenon depends on local urban characteristics.
Single cell spatial analysis identifies regulators of brain tumor initiating cells
Authors: Mirzaei Reza , D’Mello Charlotte , Liu Marina , Nikolic Ana , Kumar Mehul , Visser Frank , Bose Pinaki , Gallo Marco , Yong V. Wee 
Published: September 2022

AbstractGlioblastomas (GBMs) are aggressive brain tumors with extensive intratumoral heterogeneity. Here, we used spatial transcriptomics and single-cell ATAC-seq to dissect the transcriptome of distinct anatomical regions of the tumor microenvironment. We identified numerous extracellular matrix (ECM) molecules including biglycan elevated in areas infiltrated with brain tumor-initiating cells (BTICs). Single-cell RNA sequencing showed that the ECM molecules were differentially expressed by cells including injury response versus developmental BTICs. Exogeneous biglycan or overexpression of biglycan resulted in a higher proliferation rate of BTICs, and this was associated mechanistically with LDL receptor-related protein 6 (LRP6) binding and activation of the Wnt/β-catenin pathway. Biglycan-overexpressing BTICs grew to a larger tumor mass when implanted intracranially in mice. This study points to the spatial heterogeneity of ECM molecules in the GBM microenvironment and suggests biglycan-LRP6 axis as a therapeutic target to curb GBM growth.
Stretch-Induced Uncrimping of Equatorial Sclera Collagen Bundles
Authors: Jan Ning-Jiun , Lee Po-Yi , Wallace Jacob , Iasella Michael , Gogola Alexandra , Sigal Ian A. 
Published: September 2022

AbstractStretch-induced collagen uncrimping underlies the nonlinear mechanical behavior of the sclera according to what is often called the process of recruitment. We recently reported experimental measurements of sclera collagen crimp and pressure-induced uncrimping. Our studies, however, were cross-sectional, providing statistical descriptions of crimp with no information on the effects of stretch on specific collagen bundles. Data on bundle-specific uncrimping is necessary to better understand the effects of macroscale input on the collagen microscale and tissue failure. Our goal in this project was to measure bundle-specific stretch-induced collagen uncrimping of sclera. Three goat eyes were cryosectioned sagittally (30μm). Samples of equatorial sclera were isolated, mounted to a custom uniaxial stretcher and imaged with polarized light microscopy at various levels of clamp-to-clamp stretch until failure. At each stretch level, local strain was measured using image tracking techniques. The level of collagen crimping was determined from the bundle waviness, defined as the circular standard deviation of fiber orientation along a bundle. Eye-specific recruitment curves were then computed using eye-specific waviness at maximum stretch before sample failure to define fibers as recruited. Nonlinear mixed effect models were used to determine the associations of waviness to local strain and recruitment to clamp-to-clamp stretch. Waviness decreased exponentially with local strain (p<0.001), whereas bundle recruitment followed a sigmoidal curve with clamp-to-clamp stretch (p<0.001). Individual bundle responses to stretch varied substantially, but recruitment curves were similar across sections and eyes. In conclusion, uniaxial stretch caused measurable bundle-specific uncrimping, with the sigmoidal recruitment pattern characteristic of fiber-reinforced soft tissues.
Histopathological characteristics of different parts of surgical specimens of UPJ stenosis
Authors: TuErdi NaFeisha , Bai Junbo , Liu Kaifang , Liu Shuai , Xiong Hongxing , Gao Yu , Li Jia 
Published: September 2022

AbstractObjectiveTo observe the pathological changes of different anatomical sites in the specimens obtained from ureteropelvic junction obstruction (UPJO) caused by UPJ stenosis.Materials and MethodsA total of 34 cases of UPJO were performed. The lesion of the ureteropelvic junction was visualized as the center, the 1.5cm renal pelvis segment was taken along the upper edge of the lesion segment (as the control group). Along the lower edge of the ureteral stricture, 1cm of ureteral stricture tissue was taken downward. Different dyeing methods were used to observe the tissue arrangement of different parts, the ratio of muscle to fiber tissue and the distribution of interstitial cells of Cajal(ICC) .ResultsThe number of ICCs in the lesion segment was reduced or even absent, disordered arrangement of muscle tissue was seen, the fibrous tissue proliferated to varying degrees. The pathological changes were statistically different from those of normal segment and ureteral stricture segment.ConclusionThe decrease of ICCs cells and the degree of tissue fibrosis are closely related to the pathogenesis and disease progression of UPJO caused by UPJ stenosis.
Seq2Neo: a comprehensive pipeline for cancer neoantigen immunogenicity prediction
Authors: Diao Kaixuan , Chen Jing , Wu Tao , Wang Xuan , Wang Guangshuai , Sun Xiaoqin , Zhao Xiangyu , Wu Chenxu , Wang Jinyu , Yao Huizi , Gerarduzzi Casimiro , Liu Xue-Song 
Published: September 2022

AbstractNeoantigens derived from somatic DNA alterations are ideal cancer-specific targets. In recent years, the combination therapy of PD-1/PD-L1 blockers and neoantigen vaccines shows clinical efficacy in original PD-1/PD-L1 blocker non-responders. However, not all somatic DNA mutations can result in immunogenicity in cancer cells, and efficient tools for predicting the immunogenicity of neoepitope are still urgently needed. Here we present the Seq2Neo pipeline, which provides a one-stop solution for neoepitope features prediction from raw sequencing data, and neoantigens derived from different types of genome DNA alterations, including point mutations, insertion deletions, and gene fusions are supported. Importantly a convolutional neural networks (CNN) based model has been trained to predict the immunogenicity of neoepitope. And this model shows improved performance compared with currently available tools in immunogenicity prediction in independent datasets. We anticipate that the Seq2Neo pipeline will become a useful tool in prediction of neoantigen immunogenicity and cancer immunotherapy. Seq2Neo is an open-source software under an academic free license (AFL) v3.0 and it is freely available athttps://github.com/XSLiuLab/Seq2Neo.
Characterization of a novel gene-environment-based animal model to study resilience and susceptibility to PTSD and co-morbid depression
Authors: Iglesias Lia Parada , Coelho Arthur Alves , da Silva Nicole Rodrigues , Müller Heidi K. , Moreira Fabricio A. , Wegener Gregers , Joca Sâmia 
Published: September 2022

ABSTRACTBACKGROUNDPost-traumatic stress disorder (PTSD) and co-morbid depression are frequently associated with severe symptoms, poor response to treatment and worse prognosis. Due to the absence of a suitable animal model, little is known about the biological basis of the comorbidity, severely limiting the discovery of new and more effective treatment options. The Flinders Sensitive Line rats (FSL) is a well-validated, selectively bred animal model of depression. However, several of its features, such as cognitive deficits and altered hypothalamic-pituitary-adrenal (HPA) axis response, also match symptomatic clusters of PTSD. In parallel, its resistant counterpart, the Flinders Resistant Line (FRL), is extensively used as a simple control. Still, little is known about its performance compared to the original strain, Sprague Dawley (SD), from which the FSL/FRL was originally derived.AIMSCharacterizing the behavioural performance and mechanisms involved in FSL, FRL and SD rats in fear-memory paradigms.METHODSFSL, SD and FRL animals were submitted to tests assessing hippocampal-dependent and fear-related memory. Subsequently, plasticity factors and endocrine responses to stress were analysed to elucidate the molecular basis for the observed behavioural alterations.RESULTSWe found that FRL animals presented intact recognition memory and innate fear responses but could not properly display conditioned responses in the Conditioned Fear Conditioning (CFC) paradigm. FSL animals, despite a poor performance in the Novel Object Recognition task (NOR), showed similar levels of conditioned responses compared to SD, but impairments in extinction learning, a feature highly related to PTSD. The behavioural alterations were accompanied by alterations in plasma corticosterone levels and hippocampal expression of the glucocorticoid receptor and FKBP51.CONCLUSIONFor the first time, we demonstrate an animal model of resilience and vulnerability to PTSD and co-morbid depression. The results suggest that the endophenotypes may be based on aberrant endocrine stress responses in the hippocampus.
Impairment of sugar transport in the vascular system acts on nitrogen remobilisation and nitrogen use efficiency in Arabidopsis
Authors: Hoffmann Beate , Aubry Emilie , Marmagne Anne , Dinant Sylvie , Chardon Fabien , Le Hir Rozenn 
Published: September 2022

AbstractThe carbon (C) and nitrogen (N) metabolisms have long been known to be coupled, and this is required for adjusting nitrogen use efficiency. Despite this intricate relationship, it is still unclear how a deregulation of sugar transport impacts N allocation. Here we investigated, in Arabidopsis, the consequences of the simultaneous downregulation of the genes coding for the sugar transporters SWEET11, SWEET12, SWEET16, and SWEET17 genes on various anatomical and physiological traits ranging from the stem’s vascular system development, plant biomass production, seed yield, and N remobilisation and use efficiency. Our results show that intracellular sugar exchanges mediated by SWEET16 and SWEET17 proteins specifically impact the vascular development but do not play a significant role in the distribution of N. Most importantly, we showed that the double mutant swt11swt12, which is also impacted in the vascular development, displays an improved nitrogen use efficiency and nitrogen remobilisation to the seeds. In addition, a significant negative correlation between sugar and amino acids contents and the inflorescence stem radial growth exists, highlighting the complex interaction between the maintenance of C/N homeostasis and the inflorescence stem development. Our results thus deepen the link between sugar transport, C/N allocation and vascular system development.HighlightThe disruption of genes coding for SWEET11 and SWEET12 sugar transporters negatively impacts the stem development but improves the plant nitrogen use efficiency and nitrogen remobilisation to the seeds.
The trophic pyramid revisited: most animal classes have more predator than herbivore species
Authors: Klein Tamir , Livne-Luzon Stav , Moran Uri 
Published: September 2022

AbstractAccording to the trophic pyramid, a large array of herbivores (primary consumers) feed an increasingly narrower array of predators, from secondary consumers to top predators. However, the partitioning between herbivory and predation across the animal kingdom has not yet been tested at the global scale.Here, we use a survey of 33,762 animal species across ten major taxonomic groups (five vertebrates and five invertebrates) to partition food sources at the class and phylum levels. We use this partitioning, together with class-level biomass estimates, to create a global trophic pyramid of biomass.We show that: (1) the diet of eight of the ten groups of animals is dominated by prey rather than plants, accounting for 64-99% of the diet mass; (2) collectively across the terrestrial and marine environments, secondary consumers (invertivores; ∼1200 Mt C) have higher biomass than primary consumers (herbivores; ∼500 Mt C); (3) the two major exceptions, feeding mostly on plants, are mammals and insects; the latter form the major food source for terrestrial animals.For animal species in most classes, plants are not a food source, but rather invertebrates, mostly arthropods. Secondary consumers (invertivores) link primary consumers and top predators, and are hence pivotal to almost all food-webs.
Recombinant protein condensation inside E. coli enables the development of building blocks for bioinspired materials engineering – biomimetic spider silk protein as a case study
Authors: Gabryelczyk Bartosz , Sammalisto Fred-Eric , Gandier Julie-Anne , Feng Jianhui , Beaune Grégory , Timonen Jaakko V. I. , Linder Markus 
Published: September 2022

AbstractRecombinant expression of proteins destined to form biological materials often results in poor production yields or loss of their function due to premature aggregation. Recently, liquid-liquid phase separation has been proposed as a mechanism to control protein solubility during expression and accumulation in the cytoplasm. Here, we investigate this process in vivo during the recombinant overexpression of the spider silk-mimetic mini-spidroin NT2RepCT in Escherichia coli. The protein forms intracellular liquid-like condensates that shift to a solid-like state triggered by a decrease in their microenvironmental pH. These features are also maintained in the purified sample in vitro both in the presence of a molecular crowding agent mimicking the bacterial intracellular environment, and during a biomimetic extrusion process leading to fiber formation. Overall, we demonstrate that characterization of protein condensates inside E. coli could be used as a basis for selecting proteins for both materials applications and their fundamental structure-function studies.