bluuebunny/crossref_metadata_2025 huggingface dataset:
Chilean bee diversity: Contrasting patterns of species and phylogenetic turnover along a large-scale ecological gradient
Authors: Marshall Leon , Ascher John S. , Villagra Cristian , Beaugendre Amaury , Herrera Valentina , Henríquez-Piskulich Patricia , Vera Alejandro , Vereecken Nicolas J.
Published: September 2022

Chile’s isolation and varied climates have driven the evolution of a unique biodiversity with a high degree of endemism. The Mediterranean-type biome of Central Chile is one of 35 global biodiversity hotspots and has been highlighted as one of Chile’s most endangered areas. It is threatened by anthropogenic land use change impacting the integrity of local biomes and associated species. This area holds the most extensive collections of the country with high endemicity regarding native bee species. Characterising habitat requirements of bees is a pressing priority to safeguard them and the ecosystem services they provide.

We investigated broad-scale patterns of bee diversity using newly accessible expert-validated datasets comprising digitized specimen records from both Chilean and US collections and novel, expert-validated type specimen data for the bees of Chile. We used a generalised dissimilarity modelling (GDM) approach to explore both compositional and phylogenetic β-diversity patterns across latitudinal, altitudinal, climate and habitat gradients in well-sampled bee assemblages in Central Chile. Using the GDM measures of increasing compositional and environmental dissimilarity we categorised and compared the most important drivers of these patterns and used them to classify ‘wild bee ecoregions’ (WBE) representing unique assemblages.

Turnover of bee assemblages was explained primarily by latitudinal variation (proxy for climate) along Chile. However, temperature variations, precipitation and the presence of bare soil also significantly explained the observed patterns. In comparison, we observed less turnover in phylogenetic biodiversity corresponding to spatial gradients. We were able to develop sixde novoecoregions (WBE) all with distinct taxa, endemic lineages, and representative species. The WBE represent distinct spatial classifications but have similarities to existing biogeographical classifications, ecosystems and bioclimatic zones.

This approach establishes the baseline needed to prioritise bee species conservation efforts across this global biodiversity hotspot. We discuss the novelty of this classification considering previous biogeographical characterisations and its relevance for assessing conservation priorities for bee conservation. We argue that Chile’s WBE show areas requiring funding for bee species exploration and description, distribution mapping and strengthening of conservation policies.
Suggesting disease associations for overlooked metabolites using literature from metabolic neighbours
Authors: Delmas M. , Filangi O. , Duperier C. , Paulhe N. , Vinson F. , Rodriguez-Mier P. , Giacomoni F. , Jourdan F. , Frainay C.
Published: September 2022

In human health research, metabolic signatures extracted from metabolomics data are a strong-added value for stratifying patients and identifying biomarkers. Nevertheless, one of the main challenges is to interpret and relate these lists of discriminant metabolites to pathological mechanisms. This task requires experts to combine their knowledge with information extracted from databases and the scientific literature.

However, we show that a large fraction of metabolites are rarely or never mentioned in the literature. Consequently, these overlooked metabolites are often set aside and the interpretation of metabolic signatures is restricted to a subset of the significant metabolites. To suggest potential pathological phenotypes related to these understudied metabolites, we extend the ‘guilt by association’ principle to literature information by using a Bayesian framework. With this approach, we suggest more than 35,000 associations between 1,047 overlooked metabolites and 3,288 diseases (or disease families). All these newly inferred associations are freely available on the FORUM ftp server (See information at https://github.com/eMetaboHUB/Forum-LiteraturePropagation.).
TheAphelenchoidesgenomes reveal substantial horizontal gene transfers in the last common ancestor of free-living and major plant parasitic nematodes
Authors: Lai Cheng-Kuo , Lee Yi-Chien , Ke Huei-Mien , Lu Min R , Liu Wei-An , Lee Hsin-Han , Liu Yu-Ching , Yoshiga Toyoshi , Kikuchi Taisei , Chen Peichen J. , Tsai Isheng Jason
Published: September 2022

Aphelenchoides besseyiis a plant-parasitic nematode (PPN) in the Aphelenchoididae family capable of infecting more than 200 plant species.A. besseyiis also a species complex with strains exhibiting varying pathogenicity to plants. We present the genome and annotations of sixAphelenchoidesspecies, four of which belonged to theA. besseyispecies complex. MostAphelenchoidesgenomes have a size of 44.7-47.4 Mb and are amongst the smallest in clade IV, with the exception ofA. fujianensis, which has a size of 143.8 Mb and is the largest. Phylogenomic analysis successfully delimited the species complex intoA. oryzaeandA. pseudobesseyiand revealed a reduction of transposon elements in the last common ancestor ofAphelenchoides. Synteny analyses between reference genomes indicated that three chromosomes inA. besseyiwere derived from fission and fusion events. A systematic identification of horizontal gene transfer (HGT) genes across 27 representative nematodes allowed us to identify two major episodes of acquisition corresponding to the last common ancestor of clade IV or major PPNs, respectively. These genes were mostly lost and differentially retained between clades or strains. Most HGT events were acquired from bacteria, followed by fungi, and also from plants; plant HGT was especially prevalent inBursaphelenchus mucronatus. Our results comprehensively improve the understanding of horizontal gene transfer in nematodes.
Reduced coenzyme Q synthesis confers non-target site resistance to the herbicide thaxtomin A
Authors: Casey Chloe , Köcher Thomas , Champion Clément , Jandrasits Katharina , Mosiolek Magdalena , Bonnot Clémence , Dolan Liam
Published: September 2022

Herbicide resistance in weeds is a growing threat to global crop production. Non-target site resistance is problematic because a single resistance allele can confer tolerance to many herbicides (cross resistance), and it is often a polygenic trait so it can be difficult to identify the molecular mechanisms involved. Most characterized molecular mechanisms of non-target site resistance are caused by gain-of-function mutations in genes from a few key gene families – the mechanisms of resistance caused by loss-of-function mutations remain unclear. In this study, we first show that the mechanism of non-target site resistance to the herbicide thaxtomin A conferred by loss-of-function of the genePAM16is conserved inMarchantia polymorpha, validating its use as a model species with which to study non-target site resistance. To identify mechanisms of non-target site resistance caused by loss-of-function mutations, we generated 107UV-B mutagenizedM. polymorphaspores and screened for resistance to the herbicide thaxtomin A. We isolated 13 thaxtomin A-resistant mutants and found that 3 mutants carried candidate resistance-conferring SNPs in the MpRTN4IP1Lgene. Mprtn4ip1lmutants are defective in coenzyme Q biosynthesis and accumulate higher levels of reactive oxygen species (ROS) than wild-type plants. Mutants are also defective in thaxtomin A metabolism, consistent with the hypothesis that loss of MpRTN4IP1Lfunction confers non-target site resistance. We conclude that loss of MpRTN4IP1Lfunction is a novel mechanism of non-target site herbicide resistance, and propose that other mutations which increase ROS levels or decrease thaxtomin A metabolism could confer thaxtomin A resistance in the field.

AUTHOR SUMMARY

Modern agriculture relies on herbicides to control weed populations. However, herbicide resistance in weeds threatens the efficacy of herbicides and global crop production, similar to how antibiotic resistance poses a global health threat. Understanding the molecular mechanisms behind herbicide resistance helps to prevent resistance from evolving and to better manage herbicide resistant weeds in the field. Here, we use a forward genetic approach in the model speciesMarchantia polymorphato discover novel mechanisms of herbicide resistance. We report the discovery of a novel mechanism of herbicide resistance caused by loss-of-function mutations in the MpRTN4IP1Lgene. We find that Mprtn4ip1lmutants are resistant to the herbicides thaxtomin A and isoxaben, accumulate higher levels of reactive oxygen species than wild type plants, and are defective in thaxtomin A metabolism. We predict that loss-of-function mutations or treatments that increase reactive oxygen species production could contribute to thaxtomin A tolerance.
Major Histocompatibility Complex class I heavy chains localize in both cytoplasmic and nuclear compartment
Authors: Gómez-Herranz Maria , Dziadosz Alicja , Mikac Sara , Rychłowski Michał , Fahraeus Robin , Marek-Trzonkowska Natalia , Chruściel Elżbieta , Urban-Wójciuk Zuzanna , Papak Ines , Arcimowicz Łukasz , Marjanski Tomasz , Rzyman Witold , Sznarkowska Alicja
Published: September 2022

The Major Histocompatibility Complex class I (MHC-I) molecules present antigenic peptides (AP) to CD8+T cells for self versus non-self recognition. Loading of AP on MHC-I takes place in the endoplasmic reticulum (ER), upon shuttling of cytoplasmic AP substrates to the ER. Understanding of this process has been influenced by the view that MHC-I antigens are produced from the proteasomal degradation of cellular proteins. Recent observations on the intronic and untranslated region-derived peptides as well as on the non-AUG translation products presented on the MHC-I open the possibility that antigenic peptides can derive from pre-spliced mRNAs translated in the nuclear compartment. In this brief report, we show that a fraction of human MHC-I molecules (human leukocyte antigens type A, HLA-A) is present in the nuclei of cells, in the proximity of histone H2B. With this finding, we hope to initiate a new direction of research on the nuclear role of MHC-I and ask whether the loading of antigens can take place in the nuclear compartment.
Genomic erosion in the assessment of species extinction risk and recovery potential
Authors: van Oosterhout Cock , Speak Samuel A. , Birley Thomas , Bortoluzzi Chiara , Percival-Alwyn Lawrence , Urban Lara H. , Groombridge Jim J. , Segelbacher Gernot , Morales Hernán E.
Published: September 2022

Many species are facing unprecedented population size declines and deterioration of their environment. This exposes species to genomic erosion, which we define here as the damage inflicted to a species’ genome or gene pool due to a loss of genetic diversity, an increase in expressed genetic load, maladaptation, and/or genetic introgression. The International Union for Conservation of Nature (IUCN) bases its extinction risk assessments on direct threats to population size and habitat. However, it does not assess the long-term impacts of genomic erosion, and hence, it is likely to underestimate the extinction risk of many species. High-quality whole genome sequence data that is currently being generated could help improve extinction risk assessments. Genomic data contains information about a species’ past demography, its genome-wide genetic diversity, the incidence of genetic introgression, as well as the genetic load of deleterious mutations. Computer modelling of these data enables forecasting of population trajectories under different management scenarios. In this Perspective, we discuss the threats posed by genomic erosion. Using evolutionary genomic simulations, we argue that whole genome sequence data provides critical information for assessing the extinction risk and recovery potential of species. Genomics-informed assessments of the extinction risk complement the IUCN Red List, and such genomics-informed conservation is invaluable in guiding species recovery programs in the UN’s Decade on Ecosystem Restoration and beyond.
Allelic and Gene Dosage Effects Involving Uromodulin Aggregates Drive Autosomal Dominant Tubulointerstitial Kidney Disease
Authors: Schiano Guglielmo , Lake Jennifer , Mariniello Marta , Schaeffer Céline , Harvent Marianne , Rampoldi Luca , Olinger Eric , Devuyst Olivier
Published: September 2022

Missense mutations in theUMODgene encoding uromodulin cause autosomal dominant tubulointerstitial kidney disease (ADTKD), one of the most common monogenic kidney diseases. A pressing need for ADTKD is to bridge the gap between postulated gain-of-function mutations and organ damage - a prerequisite for therapeutic development. Based on two missenseUMODmutations associated with divergent progression of ADTKD, we generatedUmodC171YandUmodR186Sknock-in mice that showed strong allelic and gene dosage effects, with distinct dynamic pathways impacting on uromodulin trafficking, formation of intracellular aggregates, activation of ER stress, unfolded protein and immune responses, kidney damage and progression to kidney failure. Deletion of the wild-typeUmodallele in heterozygousUmodR186Smice increased the formation of uromodulin aggregates and ER stress, indicating a protective role of wild-type uromodulin. Studies in kidney tubular cells confirmed biochemical differences between distinct uromodulin aggregates, with activation of specific quality control and clearance mechanisms. Enhancement of autophagy by starvation and mTORC1 inhibition decreased the uromodulin aggregates, suggesting a therapeutic strategy. These studies substantiate a model for allelic effects and the role of toxic aggregates in the progression of ADTKD-UMOD, with relevance for toxic gain-of-function mechanisms and for strategies to improve clearance of mutant uromodulin.
SynBOLD-DisCo: Synthetic BOLD images for distortion correction of fMRI without additional calibration scans
Authors: Yu Tian , Cai Leon Y. , Morgan Victoria L. , Goodale Sarah E. , Englot Dario J. , Chang Catherine E. , Landman Bennett A. , Schilling Kurt G.
Published: September 2022

The blood oxygen level dependent (BOLD) signal from functional magnetic resonance imaging (fMRI) is a noninvasive technique that has been widely used in research to study brain function. However, fMRI suffers from susceptibility-induced off resonance fields which may cause geometric distortions and mismatches with anatomical images. State-of-the-art correction methods require acquiring reverse phase encoded images or additional field maps to enable distortion correction. However, not all imaging protocols include these additional scans and thus cannot take advantage of these susceptibility correction capabilities. As such, in this study we aim to enable state-of-the-art distortion correction with FSL’s topup algorithm of historical and/or limited fMRI data that include only a structural image and single phase encoded fMRI. To do this, we use 3D U-net models to synthesize undistorted fMRI BOLD contrast images from the structural image and use this undistorted synthetic image as an anatomical target for distortion correction with topup. We evaluate the efficacy of this approach, named SynBOLD-DisCo (synthetic BOLD images for distortion correction), and show that BOLD images corrected using our approach are geometrically more similar to structural images than the distorted BOLD data and are practically equivalent to state-of-the-art correction methods which require reverse phase encoded data. Future directions include additional validation studies, integration with other preprocessing operations, retraining with broader pathologies, and investigating the effects of spin echo versus gradient echo images for training and distortion correction. In summary, we demonstrate SynBOLD-DisCo corrects distortion of fMRI when reverse phase encoding scans or field maps are not available.
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

Spiny 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

Major 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

Statins 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

Urbanisation 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

Glioblastomas (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

Stretch-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

Objective

To observe the pathological changes of different anatomical sites in the specimens obtained from ureteropelvic junction obstruction (UPJO) caused by UPJ stenosis.

Materials and Methods

A 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) .

Results

The 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.

Conclusion

The 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

Neoantigens 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

BACKGROUND

Post-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.

AIMS

Characterizing the behavioural performance and mechanisms involved in FSL, FRL and SD rats in fear-memory paradigms.

METHODS

FSL, 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.

RESULTS

We 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.

CONCLUSION

For 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

The 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.

Highlight

The 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

According 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

Recombinant 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.
Genomic variation during culture-adaptation of genetically complexPlasmodium falciparumclinical isolates
Authors: Claessens Antoine , Stewart Lindsay B. , Drury Eleanor , Ahouidi Ambroise D. , Amambua-Ngwa Alfred , Diakite Mahamadou , Kwiatkowski Dominic P. , Awandare Gordon A. , Conway David J.
Published: September 2022

Experimental studies on the biology of malaria parasites have been mostly based on laboratory-adapted lines, but there is limited understanding of how these may differ from parasites in natural infections. Loss-of-function mutants have previously been shown to emerge during culture of somePlasmodium falciparumclinical isolates, in analyses that focused on single-genotype infections. The present study included a broader array of isolates, mostly representing multiple-genotype infections which are more typical in areas where malaria is highly endemic. Genome sequence data from multiple time points during several months of culture adaptation of 28 West African isolates were analysed, including previously available sequences along with new genome sequences from additional isolates and timepoints. Some genetically complex isolates eventually became fixed over time to single surviving genotypes in culture, whereas others retained diversity although proportions of genotypes varied over time. Drug-resistance allele frequencies did not show overall directional changes, suggesting that resistance-associated costs are not the main causes of fitness differences among parasites in culture. Loss-of-function mutants emerged during culture in several of the multiple-genotype isolates, affecting genes (includingAP2-HS, EPACandSRPK1) for which loss-of-function mutants were previously seen to emerge in single-genotype isolates. Parasite clones were derived by limiting dilution from six of the isolates, and sequencing identifiedde novovariants not detected in the bulk isolate sequences. Interestingly, most of these were nonsense mutants and frameshifts disrupting the coding sequence ofEPAC, the gene with the largest number of independent nonsense mutants previously identified in laboratory-adapted lines. Analysis of Identity-By-Descent to explore relatedness among clones revealed co-occurring non-identical sibling parasites, illustrative of the natural genetic structure within parasite populations.
Arabidopsis DXO1 affects the processing of precursors of cytoplasmic and chloroplast ribosomal RNA
Authors: Zakrzewska-Placzek Monika , Kwasnik Aleksandra , Krzyszton Michal , Golisz-Mocydlarz Anna , Kufel Joanna
Published: September 2022

Decapping 5’-3’ exoribonucleases from the DXO/Rai1 family, are highly conserved among eukaryotes and exhibit diverse enzymatic activities depending on the organism. The biochemical and structural properties of the plant DXO1 differ from the yeast and animal counterparts, which is reflected in the in vivo functions of this enzyme. Here we show that Arabidopsis DXO1 contributes to the efficient processing of rRNA precursors in both nucleolar/cytosol and chloroplast maturation pathways. However, processing defects in DXO1-deficient plants do not depend on the catalytic activity of the enzyme but rely on its plant-specific N-terminal extension. Our RNA sequencing analyses show that the dxo1 mutation deregulates the expression of many ribosomal protein genes, most likely leading to inefficient or delayed pre-rRNA maturation. Strikingly, some of the observed molecular and morphological phenotypes of dxo1 plants are suppressed by the knock-down of XRN3, providing evidence for functional interaction between DXO1 and XRN proteins.

HIGHLIGHT

Arabidopsis DXO1 protein regulates the expression of genes encoding ribosomal proteins and contributes to the correct processing of ribosomal RNA precursors.
The mushroom body output encodes behavioral decision during sensory-motor transformation
Authors: Arican Cansu , Johannes Schmitt Felix , Rössler Wolfgang , Strube-Bloss Martin Fritz , Nawrot Martin Paul
Published: September 2022

Animal behavioral decisions are dynamically formed by evaluating momentary sensory evidence on the background of individual experience and the acute motivational state. In insects, the mushroom body (MB) has been implicated in forming associative memories and in assessing the appetitive or aversive valence of sensory stimuli to bias approach versus avoidance behavior. To study the MB involvement in innate feeding behavior we performed extracellular single-unit recordings from MB output neurons (MBONs) while simultaneously monitoring a defined feeding behavior in response to timed odor stimulation in naïve cockroaches. All animals expressed the feeding behavior almost exclusively in response to food odors. Likewise, MBON responses were invariably and strongly tuned to the same odors. Importantly, MBON responses were restricted to behaviorally responded trials, which allowed the accurate prediction of the occurrence versus non-occurrence of the feeding behavior in individual trials from the neuronal population activity. During responded trials the neuronal activity generally preceded the onset of the feeding behavior, indicating a causal relation. Our results contest the predominant view that MBONs encode stimulus valence. Rather, we conclude that the MB output dynamically encodes the behavioral decision to inform downstream motor networks.
Ultraviolet radiation and dehydration stress induce overlapping transcriptional and metabolic responses in Syntrichia mosses
Authors: Ekwealor Jenna T. B. , Kosina Suzanne , Bowen Benjamin P. , Silva Anderson T. , Northen Trent , Oliver Melvin J. , Mishler Brent D.
Published: September 2022

Protection from excess solar radiation and access to sufficient water are important problems for terrestrial plants to solve. Desiccation tolerance (DT), defined as the ability to equilibrate to dry air and resume normal metabolic activity after rehydration, allows organisms to survive dry periods by limiting metabolic activity to periods of moisture availability. We compared separate and combined effects of chronic ultraviolet radiation (UVR) treatments (UV-A and UV-A/B) and a dehydration treatment (as a surrogate for desiccation) in the mosses Syntrichia ruralis and S. caninervis to uncover the nature of correlation between DT and UVR tolerance (UVRT).

Using a fully factorial experiment with combined transcriptomics and metabolomics, we tested for cross-talk (overlap in signaling pathways in response to different stressors but separate mechanisms of protection) in the genetic underpinnings of DT and UVRT and cross-tolerance (overlap in the mechanism of protection) these two stressors.

Shared transcriptomic response to the two stressors with no significant interaction between them suggested cross-talk between UVRT and DT for S. caninervis. Phenolic metabolites and transcripts were involved in the response to UVR and dehydration in both species.

Some candidate UVRT genes and metabolites were induced by UVR in S. ruralis, but not S. caninervis, supporting the hypothesis that S. ruralis has a more plastic, acclimatable UVR response than S. caninervis, and that these differences are predictable by their unique interaction with these stressors as poikilohydric organisms.
Cryogenic electron tomography reveals novel structures in the apical complex of Plasmodium falciparum
Authors: Sun Stella Y. , Segev-Zarko Li-av , Pintilie Grigore D. , Kim Chi Yong , Staggers Sophia R. , Schmid Michael F. , Egan Elizabeth S. , Chiu Wah , Boothroyd John C.
Published: September 2022

Intracellular infectious agents, like the malaria parasite, Plasmodium falciparum, face the daunting challenge of how to invade a host cell. This problem may be even harder when the host cell in question is the enucleated red blood cell. Evolution has provided P. falciparum and related single-celled parasites within the phylum Apicomplexa with a collection of organelles at their apical end that mediate invasion. This apical complex includes at least two sets of secretory organelles, micronemes and rhoptries, and several structural features like apical rings and a putative pore through which proteins may be introduced into the host cell during invasion. In this paper, we perform cryogenic electron tomography (cryo-ET) on isolated merozoites to visualize the apical machinery. Through tomography reconstruction of cellular compartments, we see new details of known structures like the rhoptry tip interacting directly with a rosette resembling the recently described rhoptry-secretory-apparatus (RSA), or with an apical vesicle docked beneath the RSA. Subtomogram averaging reveals that the apical rings have a fixed number of repeating units, each of which is similar in overall size and shape to the units in the apical rings of tachyzoites of Toxoplasma gondii. Comparison of these polar rings in Plasmodium and Toxoplasma parasites also reveals them to have a structurally conserved assembly patterning. These results provide new insight into the essential features of this remarkable machinery used by apicomplexan parasites to invade their respective host cells.