bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mathematical modelling of fracture waves in a blocky medium with thin compliant interlayers
Authors: Sadovskaya Oxana V. , Sadovskii Vladimir M. 
Published: June 2024

Physical mechanisms that contribute to the generation of fracture waves in condensed media under intensive dynamic impacts have not been fully studied. One of the hypotheses is that this process is associated with the blocky structure of a material. As the loading wave passes, the compliant interlayers between blocks are fractured, releasing the energy of self-balanced initial stresses in the blocks, which supports the motion of the fracture wave. We propose a new efficient numerical method for the analysis of the wave nature of the propagation of a system of cracks in thin interlayers of a blocky medium with complex rheological properties. The method is based on a variational formulation of the constitutive relations for the deformation of elastic–plastic materials, as well as the conditions for contact interaction of blocks through interlayers. We have developed a parallel computational algorithm that implements this method for supercomputers with cluster architecture. The results of the numerical simulation of the fracture wave propagation in tempered glass under the action of distributed pulse disturbances are presented.
This article is part of the theme issue 'Non-smooth variational problems with applications in mechanics'.
Coevolutionary hotspots favour dispersal and fuel biodiversity in mutualistic landscapes under environmental changes
Authors: Cosmo Leandro G. , Acquaviva Julia N. , Guimarães Jr. Paulo R. , Pires Mathias M. 
Published: June 2024

Mutualistic interactions are key to sustaining Earth’s biodiversity. Yet, we are only beginning to understand how coevolution in mutualistic assemblages can shape the distribution and persistence of species across landscapes. Here, we combine the geographic mosaic theory of coevolution with metacommunity dynamics to understand how geographically structured selection can shape patterns of richness, dispersal, extinction and persistence of mutualistic species. In this model, species may experience strong or weak reciprocal selection imposed by mutualisms within each patch (i.e. hotspots and coldspots, respectively). Using numerical simulations, we show that mutualistic coevolution leads to a concentration of species richness at hotspots. Such an effect occurs because hotspots sustain higher rates of colonization and lower rates of extinction than coldspots, whether the environment changes or not. Importantly, under environmental changes, coldspots fail to sustain a positive colonization-to-extinction balance. Rather, species persistence within coldspots relies on hotspots acting as biodiversity sources and enhancing population dispersal across the landscape. In fact, even a few hotspots in the landscape can fuel the spatial network of dispersal of populations in the metacommunity. Our study highlights that coevolutionary hotspots can act as biodiversity sources, favouring colonization and allowing species to expand their distribution across landscapes even in changing environments.
This article is part of the theme issue ‘Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics’.
Induction of territorial behavior and dominance hierarchies in laboratory mice
Authors: Battivelli Dorian , Boldrini Lucas , Jaiswal Mohit , Patil Pradnya , Torchia Sofia , Engelen Elizabeth , Spagnoletti Luca , Kaspar Sarah , Gross Cornelius T. 
Published: June 2024

AbstractTerritorial behaviors comprise a set of coordinated actions and response patterns found across animal species that promote the exclusive access to resources. House mice are highly territorial with a subset of males consistently attacking and chasing competing males to expel them from their territories and performing urine marking behaviors to signal the extent of their territories. Natural variation in territorial behaviors within a mouse colony leads to the formation of dominance hierarchies in which subordinate males can reside within the territory of a dominant male. While the full repertoire of such territorial behaviors and hierarchies has been extensively studied in wild-derived mice in semi-natural enclosures, so far they have not been established in the smaller enclosures and with the genetically-defined laboratory strains required for the application of neural recording and manipulation methods. Here, we present a protocol to induce an extensive repertoire of territorial behaviors in small enclosures in laboratory mice, including a method for the simultaneous tracking of urine marking behavior in mouse pairs. Using this protocol we describe the emergence of robust dominant-subordinate hierarchies between pairs of CD1 outbred or CD1xB6 F1 hybrid mice, but unexpectedly not in C57BL/6 inbred animals. Our behavioral paradigm opens the door for neurocircuit studies of territorial behaviors and social hierarchy in the laboratory.
Metabolite T2relaxation times decrease across the adult lifespan in a large multi-site cohort
Authors: Hupfeld Kathleen E. , Murali-Manohar Saipavitra , Zöllner Helge J. , Song Yulu , Davies-Jenkins Christopher W. , Gudmundson Aaron T. , Simičić Dunja , Simegn Gizeaddis , Carter Emily E. , Hui Steve C. N. , Yedavalli Vivek , Oeltzschner Georg , Porges Eric C. , Edden Richard A. E. 
Published: June 2024

AbstractPurposeRelaxation correction is crucial for accurately estimating metabolite concentrations measured usingin vivomagnetic resonance spectroscopy (MRS). However, the majority of MRS quantification routines assume that relaxation values remain constant across the lifespan, despite prior evidence of T2changes with aging for multiple of the major metabolites. Here, we comprehensively investigate correlations between T2and age in a large, multi-site cohort.MethodsWe recruited approximately 10 male and 10 female participants from each decade of life: 18-29, 30-39, 40-49, 50-59, and 60+ years old (n=101 total). We collected PRESS data at 8 TEs (30, 50, 74, 101, 135, 179, 241, and 350 ms) from voxels placed in white-matter-rich centrum semiovale (CSO) and gray-matter-rich posterior cingulate cortex (PCC). We quantified metabolite amplitudes using Osprey and fit exponential decay curves to estimate T2.ResultsOlder age was correlated with shorter T2for tNAA, tCr3.0, tCr3.9, tCho, Glx, and tissue water in CSO and PCC; rs= −0.21 to −0.65, allp<0.05, FDR-corrected for multiple comparisons. These associations remained statistically significant when controlling for cortical atrophy. T2values did not differ across the adult lifespan for mI. By region, T2values were longer in the CSO for tNAA, tCr3.0, tCr3.9, Glx, and tissue water and longer in the PCC for tCho and mI.ConclusionThese findings underscore the importance of considering metabolite T2changes with aging in MRS quantification. We suggest that future 3T work utilize the equations presented here to estimate age-specific T2values instead of relying on uniform default values.
Genetic ablation of the TET family in retinal progenitor cells impairs photoreceptor development and leads to blindness
Authors: Dvoriantchikova Galina , Moulin Chloe , Fleishaker Michelle , Almeida Vania , Pelaez Daniel , Lam Byron L. , Ivanov Dmitry 
Published: June 2024

AbstractRod and cone photoreceptors are critical for vision, and their loss leads to blindness. Photoreceptors are epigenetically unique, because the promoters of the genes required for the development and function of these neurons are hypermethylated in retinal progenitor cells (RPCs) and hypomethylated in photoreceptors. However, the mechanism responsible for DNA demethylation during the differentiation of RPCs into photoreceptors and its role in photoreceptor development and function were unknown. We hypothesized that the Ten-Eleven Translocation (TET) family of dioxygenases plays a key role in this mechanism. To this end, we knocked out all TET genes in RPCs and characterized the TET-deficient and control retinas using various approaches including electron microscopy, electroretinogram (ERG) tests, RNA-seq, whole genome bisulfite sequencing (WGBS), and 5hmC-Seal. We found that genetic ablation of the TET family prevents demethylation of the promoters of genes essential for rod specification and for rod and cone maturation during the differentiation of RPCs into photoreceptors. Preservation of methylated cytosines in the promoters of these genes significantly reduced their expression, which was confirmed by western blot analysis. This impaired expression leads to the underdevelopment or complete absence of outer segments and synaptic termini in the photoreceptors of TET-deficient retinas, which results in loss of rod and cone function, as assayed by ERG. These function-deprived, underdeveloped photoreceptors die over time, which leads to blindness.
Temporal multi-omic analysis of COVID-19 in end-stage kidney disease
Authors: Stephenson Emily , Macdonald-Dunlop Erin , Dratva Lisa M , Lindeboom Rik G.H. , Tuong Zewen Kelvin , Tun Win Min , Buang Norzawani B , Ballereau Stephane , Cabantaus Mia , Peñalver Ana , Prigmore Elena , Ferdinand John R , Stewart Benjamin J , Gisby Jack , Malik Talat , Clarke Candice L , Medjeral-Thomas Nicholas , Prendecki Maria , McAdoo Stephen , Portet Anais , Willicombe Michelle , Sandhu Eleanor , Pickering Matthew C. , Botto Marina , Teichmann Sarah A. , Haniffa Muzlifah , Clatworthy Menna R. , Thomas David C. , Peters James E. 
Published: June 2024

SummaryPatients with end-stage kidney disease (ESKD) are at high risk of severe COVID-19. We performed longitudinal single cell multi-omic immune profiling of ESKD patients with COVID- 19, sampled during two waves of the pandemic. Uniquely, for a subset of patients, we obtained samples before and during acute infection, allowing intra-individual comparison. Using single- cell transcriptome, surface proteome and immunoreceptor sequencing of 580,040 high-quality cells, derived from 187 longitudinal samples from 61 patients, we demonstrate widespread changes following infection. We identified gene expression signatures of severity, with the majority of pathways differentiating mild from severe disease in B cells and monocytes. For example, gene expression ofPLAC8, a receptor known to modulate SARS-CoV-2 entry to cells, was a marker of severity in CD14+ monocytes. Longitudinal profiling demonstrated distinct temporal molecular trajectories in severe versus mild disease, including type 1 and type 2 interferon signalling,MHCgene expression and, in B cells, a proliferative signature (KRASandMYC). Evaluation of clonal T cell dynamics showed that the fastest expanding clones were significantly enriched in known SARS-CoV-2 specific sequences and shared across multiple patients. Our analyses revealed novel TCR clones likely reactive to SARS- CoV-2. Finally, we identified a population of transcriptionally distinct monocytes that emerged in peripheral blood following glucocorticoid treatment. Overall, our data delineate the temporal dynamics of the immune response in COVID-19 in a high-risk population and provide a valuable open-access resource.
An endogenous GLP-1 circuit engages VTA GABA neurons to regulate mesolimbic dopamine neurons and attenuate cocaine seeking
Authors: Merkel Riley , Hernandez Nicole , Weir Vanessa , Zhang Yafang , Rich Matthew T. , Crist Richard C. , Reiner Benjamin C. , Schmidt Heath D. 
Published: June 2024

AbstractRecent studies show that systemic administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist is sufficient to attenuate the reinstatement of cocaine-seeking behavior, an animal model of relapse. However, the neural mechanisms mediating these effects and the role of endogenous central GLP-1 signaling in cocaine seeking remain unknown. Here, we show that voluntary cocaine taking decreased plasma GLP-1 levels in rats and that chemogenetic activation of GLP-1-producing neurons in the nucleus tractus solitarius (NTS) that project to the ventral tegmental area (VTA) decreased cocaine reinstatement. Single nuclei transcriptomics and FISH studies revealed GLP-1Rs are expressed primarily on GABA neurons in the VTA. Usingin vivofiber photometry, we found that the efficacy of a systemic GLP-1R agonist to attenuate cocaine seeking was associated with increased activity of VTA GABA neurons and decreased activity of VTA dopamine neurons. Together, these findings suggest that targeting central GLP-1 circuits may be an effective strategy toward reducing cocaine relapse and highlight a novel functional role of GABAergic GLP-1R-expressing midbrain neurons in drug seeking.
Appraising the natural root-knot nematode resistance inSolanum sisymbriifolium, a wild relative of potato
Authors: Ko Itsuhiro , Caplan Allan B. , Kuhl Joseph C. , Gleason Cynthia 
Published: June 2024

SummaryRoot-knot nematodes (RKNs) are a major pest of Solanum and other economically important crops worldwide. Two species of RKNs (Meloidogyne chitwoodiandMeloidogyne hapla) are persistent threats to potato growers of the United States. These RKNs infect potato roots and tubers, causing tuber blemishes that decrease potato market value and significantly impact the profitability of the infected potato crop. Due to environmental, health, and economic concerns, the longstanding control methods of using soil fumigants and post-plant nematicides are not favored by producers and consumers. Therefore, deploying RKN resistant cultivars is an alternative method to control RKN damage. However, there is no genetic resistance to RKN in commercially-available, cultivated potatoes. Therefore, the critical first step to breed a RKN resistant plant is to identify a genetic source of RKN resistance. A wildSolanumspecies,Solanum sisymbriifolium,also known as litchi tomato, can effectively control several agronomically important species of plant parasitic nematodes.Solanum sisymbriifoliumis completely resistant to RKNs; only a few nematodes enter the plant roots and those that do, cannot establish a feeding site. To understand its ability to prevent RKNs from forming feeding sites, we performed transcriptomic analysis ofS. sisymbriifoliumroots inoculated with the Northern root knot nematode,M. hapla. Combined with the annotation of the recently publishedS. sisymbriifoliumgenome assembly, we discovered 13 differentially expressed resistance-related genes upon nematode inoculation. By transforming potatoes with candidate resistance genes fromS. sisymbriifolium, we aim to understand the strong genetic resistance inS. sisymbriifoliumand whether those genes are necessary and sufficient to drive resistance to RKN in potatoes. This information will help us understand gene functions and help us generate RKN resistance in relevantSolanumcrops.
BMP4 induces a p21-dependent cell state shift in glioblastoma linking mesenchymal transition to senescence
Authors: Niklasson Mia , Dalmo Erika , Segerman Anna , Rendo Veronica , Westermark Bengt 
Published: June 2024

AbstractBone morphogenetic protein 4 (BMP4) has emerged as a potential glioblastoma therapy due to its anti- proliferative effect via SOX2 downregulation and differentiation promotion. However, BMP4 responses vary across and within tumors. Our previous data indicate that BMP4 induces transition to a mesenchymal-like cell state. Mesenchymal transition is associated with therapy-resistance and tumor recurrence, as is senescence in cancer.In this study, we investigated BMP4’s potential to induce senescence in primary glioblastoma cells, including proneural- and mesenchymal-like clones derived from the same tumor. BMP4 treatment induced senescence-associated genes and phenotypic changes such as cell enlargement, senescence- associated-β-gal expression, lamin B1 downregulation, and elevated p21 levels. The most robust senescence induction was observed in the mesenchymal-like clone, compared to its proneural counterpart. Notably, mesenchymal-like cells displayed high basal levels of p21 and other senescence- associated markers, suggesting a convergence of mesenchymal and senescent traits. p21 knockout abolished BMP4-induced senescence, maintaining proliferation and cell size despite SOX2 downregulation. Additionally, senolytic treatment effectively eliminated senescent cells through apoptosis, thereby favoring survival of cells retaining normal p21 levels.Our findings demonstrate BMP4’s ability to induce p21-dependent senescence in glioblastoma, particularly in therapy-resistant mesenchymal-like cells. These insights provide potential therapeutic strategies targeting senescence pathways in this challenging disease.
Phosphate starvation-induced CORNICHON HOMOLOG 5 as endoplasmic reticulum cargo receptor for PHT1 transporters inArabidopsis
Authors: Chiu Chang-Yi , Tsai Cheng-Da , Wang Jhih-Yi , Tsai Ming-Hsuan , McGinness Alastair J. , Lung Hui-Fang , Kanno Satomi , Kriechbaumer Verena , Liu Tzu-Yin 
Published: June 2024

ABSTRACTPhosphate (Pi) is essential for plant growth and is acquired by the plasma membrane (PM) PHOSPHATE TRANSPORTER 1 proteins (PHT1s). Enhancing the abundance of PHT1s at the cell surface under Pi limitation thus ensures plant productivity and sustainable agriculture. CORNICHON HOMOLOG proteins (CNIHs) are conserved eukaryotic cargo receptors that mediate the selective endoplasmic reticulum (ER) export of membrane proteins. We identified theArabidopsis thaliana CNIH5(AtCNIH5) as a Pi starvation-inducible gene preferentially expressed in the outer root cell layers above the meristem.AtCNIH5 co-localizes to theAtSAR1A/AtSEC16A/AtSEC24A-labeled ER exit sites and interacts withAtPHT1;1 and PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1 (AtPHF1). Loss ofAtCNIH5confers reduced shoot Pi levels and decreasedAtPHT1s but increasedAtPHF1. The root hair and the epidermis within the transition/elongation zone of thecnih5mutant display a lower PM targeting efficiency ofAtPHT1;1. Moreover, dysfunctionalAtCNIH5 exerts a suppressive effect on the growth ofphf1and alleviates Pi toxicity in the Pi overaccumulatorpho2. However, thein vivoprotein–protein interaction and degradation assays indicated thatAtCNIH5 is not a direct target ofAtPHO2. Our findings unveil that low Pi-responsiveAtCNIH5 interplays withAtPHF1 to promote the PM targeting ofAtPHT1s in a cell type-dependent manner.
A disorder of consciousness rather than complete locked-in may be the final stage of ALS
Authors: Gobert F. , Merida I. , Maby E. , Seguin P. , Jung J. , Morlet D. , André-Obadia N. , Dailler F. , Berthomier Ch. , Otman A. , Bars D. Le , Scheiber Ch. , Hammers A. , Bernard E. , Costes N. , Bouet R. , Mattout J. 
Published: June 2024

AbstractThe end-stage of amyotrophic lateral sclerosis [ALS] is presumed to be a complete Locked-In Syndrome [cLIS], assuming an internally preserved consciousness that would not be accessible anymore from the outside. However, whether consciousness persists at this stage of ALS remains to be demonstrated. Shifting the perspective from cLIS (presupposed consciousness) to Cognitive Motor Dissociation (to-be-demonstrated consciousness), we attempted to demonstrate consciousness and communication with two cLIS-ALS patients using a multimodal awareness assessment battery. It involved complete neurophysiological assessments, passive and active auditory oddball paradigm (Subject-Own-Name/P300), an auditory-based Brain-Computer-Interface [BCI] and activation-task imaging using functional MRI or [15O]H2O PET. Wakefulness (long-term EEG), brain morphology (CT or MRI scans) and resting brain metabolism ([18F]fluoro-deoxy-glucose PET) were used to describe the underlying cLIS brain function.While Patient 1 could initially follow simple commands, he failed twice to control the BCI. At follow-up, he showed no more evidence of command following and his oddball (Own Name - P300) cognitive responses has disappeared. At his unique evaluation, Patient 2 was neither able to follow simple commands nor to control the BCI.Both patients had altered wakefulness, brain atrophy, and a global cortico-sub-cortical hypometabolism pattern compatible with a disorder of consciousness, regarded as an extreme form of an ALS-associated fronto-temporal dementia.While it is not possible to firmly demonstrate the absence of awareness, each independent measure concurred with suggesting that a “degenerative disorder of consciousness” rather than a cLIS might be the final stage of ALS. In future cases, this dramatic cognitive decline should be anticipated before communication disappears to enable precise advance directives regarding end-of-life issues in case complete – and neurophysiologically confirmed – unresponsiveness occurs.Altogether, the neuroimaging features distinguishing the mechanisms in this rare condition is a significant milestone to understand end-stage ALS. The present clinical study calls for further exploration of this terminal stage to determine the prevalence of this profile in whom communication seems hopeless.
New insights into the functions of ACBD4/5-like proteins using a combined phylogenetic and experimental approach across model organisms
Authors: Kors Suzan , Schuster Martin , Maddison Daniel C. , Kilaru Sreedhar , Schrader Tina A. , Costello Joseph L. , Islinger Markus , Smith Gaynor A. , Schrader Michael 
Published: June 2024

AbstractAcyl-CoA binding domain-containing proteins (ACBDs) perform diverse but often uncharacterised functions linked to cellular lipid metabolism. Human ACBD4 and ACBD5 are closely related peroxisomal membrane proteins, involved in tethering of peroxisomes to the ER and capturing fatty acids for peroxisomal β-oxidation. ACBD5 deficiency causes neurological abnormalities including ataxia and white matter disease. Peroxisome-ER contacts depend on an ACBD4/5-FFAT motif, which interacts with ER-resident VAP proteins. As ACBD4/5-like proteins are present in most fungi and all animals, we combined phylogenetic analyses with experimental approaches to improve understanding of their evolution and functions. Notably, all vertebrates exhibit gene sequences for both ACBD4 and ACBD5, while invertebrates and fungi possess only a single ACBD4/5-like protein. Our analyses revealed alterations in domain structure and FFAT sequences, which help understanding functional diversification of ACBD4/5-like proteins. We show that theDrosophila melanogasterACBD4/5-like protein possesses a functional FFAT motif to tether peroxisomes to the ER via Dm_Vap33. Depletion of Dm_Acbd4/5 caused peroxisome redistribution in wing neurons and reduced life expectancy. In contrast, the ACBD4/5-like protein of the filamentous fungusUstilago maydislacks a FFAT motif and does not interact with Um_Vap33. Loss of Um_Acbd4/5 resulted in an accumulation of peroxisomes and early endosomes at the hyphal tip. Moreover, lipid droplet numbers increased and mitochondrial membrane potential declined, implying altered lipid homeostasis. Our findings reveal differences between tethering and metabolic functions of ACBD4/5-like proteins across evolution, improving our understanding of ACBD4/5 function in health and disease. The need for a unifying nomenclature for ACBD proteins is discussed.