bluuebunny/crossref_metadata_2025_split huggingface dataset:
Busted: maternal modifiers of the triploid block involved in seed size control
Authors: Akinmusola Ruth Y. , Kilsby Harvey , Wilkins Catherine-Axa , Cevik Volkan , Scott Rod , Doughty James 
Published: February 2024

ABSTRACTThe triploid block leads to seed abortion in crosses involving tetraploid Col-0 pollen. The genetic basis underlying this phenomenon is established in the endosperm and attributed to parental genomic imprinting. This research utilised the genetic variation in Arabidopsis to identify the genomic regions harbouring the maternal modifiers of the triploid block to produce viable large seeds. Distinct chromosomal regions were identified in Bla-1 and Tsu-0 accessions. The Bla-1 maternal modifier maps to theTTG2locus at the lower end of chromosome 2 to produce large viable seeds in response to a triploid block. Tsu-0 accession, on the other hand, recruits theTTG1locus on the upper arm of chromosome 5 as a maternal modifier of the triploid block.TTG1andTTG2mutations significantly increased the proportion of large viable seeds in interploidy crosses. Both genes are involved in transcriptional regulation in the flavonoid biosynthesis pathway. However, to regulate seed size in diploids,TTG1functions synergistically with auxin but does so independently ofTTG2. This work contributed to the genetic framework for theTTG1andTTG2seed size roles.HIGHLIGHTSDifferent Arabidopsis accessions recruit maternal modifiers to repress Col-killing in F1triploids.These maternal modifiers may operate in the same pathway, such as the flavonoid biosynthesis pathway or other interconnected pathways such as auxin.TTG1andTTG2generally increase F1triploid survival but in an accession-dependent manner.TTG1differentially exhibits a strong positive additive interaction with auxin to increase diploid seed size.TheTTG1/TTG2roles in diploid seed size control appear to have diverged somewhere in the auxin branch of the flavonoid biosynthesis pathway.
Ovarian disrupting effects and mechanisms of long- and short-chain per- and polyfluoroalkyl substances in mice
Authors: Pattarawat Pawat , Zhan Tingjie , Fan Yihan , Zhang Jiyang , Yang Hilly , Zhang Ying , Moyd Sarahna , Douglas Nataki C. , Urbanek Margrit , Buckley Brian , Burdette Joanna , Zhang Qiang , Kim Ji-Yong Julie , Xiao Shuo 
Published: February 2024

AbstractBackgroundThe extensive use of per- and polyfluoroalkyl substances (PFAS) has led to environmental contamination and bioaccumulation. Previous research linked PFAS exposure to female reproductive disorders, but the mechanism remains elusive. Further, most studies focused on legacy long-chain PFOA and PFOS, yet the reproductive impacts of other long-chain PFAS and short-chain alternatives are rarely explored.ObjectivesWe investigated the effects and mechanisms of long- and short-chain PFAS on the ovary and associated ovarian functions.MethodsA 3Din vitroovarian follicle culture system and anin vivomouse model, together with approaches of reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, RNA-sequencing, pharmacological treatment,in situzymography, histology,in situhybridization, analytical chemistry, and benchmark dose modeling (BMD), were used to test environmentally relevant exposure levels of six long- and short-chain PFAS on follicle maturation, hormone secretion, and ovulation.ResultsIn vitroexposure revealed that long-but not short-chain PFAS interfered with gonadotropin-dependent follicle maturation, ovulation, and hormone secretion. Mechanistically, long-chain perfluorononanoic acid (PFNA) acted as a peroxisome proliferator-activated receptor gamma (PPARγ) agonist in granulosa cells to disrupt follicle-stimulating hormone (FSH)-dependent follicle maturation, luteinizing hormone (LH)-stimulated ovulation, and associated gene regulatory pathways.In vivomouse exposure confirmed the ovarian accumulation of PFNA and the mechanism of PPARγ-mediated ovarian toxicities of PFNA observedin vitro. The BMD analysis ofin vitroandin vivoresults suggested human relevant exposure levels of long-chain PFAS in our study pose an extra risk of ovarian defects, with follicular rupture as the most sensitive endpoint.DiscussionUsingin vitrofollicle culture andin vivomouse models, we discovered that long-chain PFAS interfere with gonadotropin-dependent follicle maturation, hormone secretion, and ovulation, posing a non-negligible risk to women’s reproductive health including anovulation, irregular menstrual cycles, and sub- or infertility.
Antibody-Drug Conjugates Targeting the EGFR Ligand Epiregulin Elicit Robust Anti-Tumor Activity in Colorectal Cancer
Authors: Jacob Joan , Anami Yasuaki , High Peyton , Liang Zhengdong , Subramanian Shraddha , Ghosh Sukhen C. , AghaAmiri Solmaz , Guernsey-Biddle Cara , Tran Ha , Rowe Julie H. , Azhdarinia Ali , Tsuchikama Kyoji , Carmon Kendra S. 
Published: February 2024

AbstractAs colorectal cancer (CRC) remains a leading cause of cancer-related death, identifying therapeutic targets and approaches is essential to improve patient outcomes. The EGFR ligand epiregulin (EREG) is highly expressed in RAS wildtype and mutant CRC with minimal expression in normal tissues, making it an attractive target for antibody-drug conjugate (ADC) development. In this study, we produced and purified an EREG monoclonal antibody (mAb), H231, that had high specificity and affinity for human and mouse EREG. H231 also internalized to lysosomes, which is important for ADC payload release. ImmunoPET andex vivobiodistribution studies showed significant tumor uptake of89Zr-labeled H231 with minimal uptake in normal tissues. H231 was conjugated to either cleavable dipeptide or tripeptide chemical linkers attached to the DNA-alkylating payload duocarmycin DM, and cytotoxicity of EREG ADCs was assessed in a panel of CRC cell lines. EREG ADCs incorporating tripeptide linkers demonstrated the highest potency in EREG-expressing CRC cells irrespective of RAS mutations. Preclinical safety and efficacy studies showed EREG ADCs were well-tolerated, neutralized EGFR pathway activity, caused significant tumor growth inhibition or regression, and increased survival in CRC cell line and patient-derived xenograft models. These data suggest EREG is a promising target for the development of ADCs for treating CRC and other cancer types that express high levels of EREG. While the efficacy of clinically approved anti-EGFR mAbs are largely limited by RAS mutational status, EREG ADCs may show promise for both RAS mutant and wildtype patients, thus improving existing treatment options.Significance:EREG-targeting antibody-drug conjugates demonstrate acceptable safety and robust therapeutic efficacy in RAS mutant and wildtype colorectal cancer, suggesting their potential as an alternative to EGFR-targeted therapy to benefit a broader patient population.
SpacerPlacer: Ancestral reconstruction of CRISPR arrays reveals the evolutionary dynamics of spacer deletions
Authors: Fehrenbach Axel , Mitrofanov Alexander , Alkhnbashi Omer S. , Backofen Rolf , Baumdicker Franz 
Published: February 2024

Bacteria employ CRISPR-Cas systems for defense by integrating invader-derived sequences, termed spacers, into the CRISPR array, which constitutes an immunity memory. While spacer deletions occur randomly across the array, newly acquired spacers are predominantly integrated at the leader end. Consequently, spacer arrays can be used to derive the chronology of spacer insertions.Reconstruction of ancestral spacer acquisitions and deletions could help unravel the coevolution of phages and bacteria, the evolutionary dynamics in microbiomes, or track pathogens. However, standard reconstruction methods produce misleading results by overlooking insertion order and joint deletions of spacers.Here, we present SpacerPlacer, a maximum likelihood-based ancestral reconstruction approach for CRISPR array evolution. We used SpacerPlacer to reconstruct and investigate ancestral deletion events of 4565 CRISPR arrays, revealing that spacer deletions occur 374 times more frequently than mutations and are regularly deleted jointly, with an average of 2.7 spacers. Surprisingly, we observed a decrease in the spacer deletion frequency towardsbothends of the reconstructed arrays. While the resulting trailer-end conservation is commonly observed, a reduced deletion frequency is now also detectable towards the variable leader end. Finally, our results point to the hypothesis that frequent loss of recently acquired spacers may provide a selective advantage.
The SAS Chromatin-Remodeling Complex Mediates Inflorescence-Specific Chromatin Accessibility for Transcription Factor Binding
Authors: Guo Jing , Liu Zhen-Zhen , Su Yin-Na , He Xin-Jian 
Published: February 2024

AbstractWhile the role of transcription factors in flower development is well understood, the impact of chromatin remodeling on this process remains largely unclear. We conducted a comprehensive analysis to investigate the coordination of the SAS, BAS, and MAS-type SWI/SNF chromatin-remodeling complexes with transcription factors to regulate chromatin accessibility and gene transcription during flower development inArabidopsis thaliana. Our findings indicate that the SAS complex binds to numerous genes related to flower development and is responsible for establishing chromatin accessibility of these genes during flower development. In contrast, the BAS and MAS complexes exhibit minimal involvement in regulating the accessibility of these genes. The SAS-bound genomic regions and the SAS-dependent accessible regions are enriched with sites occupied by multiple MADS family transcription factors involved in flower development. Furthermore, we found that the SAS-dependent accessibility is indispensable for the genomic binding of the MADS transcription factor AP1 at these regions. This study highlights the dynamic role of the SAS complex in modulating the genomic binding of transcription factors during plant development.One-sentence summaryThe SAS-type SWI/SNF complex regulates Inflorescence-specific chromatin accessibility at distal promoter and upstream intergenic regions, thereby facilitating the binding of transcription factors involved in flower development.
Predicting species invasiveness with genomic data: is Genomic Offset related to establishment probability?
Authors: Camus Louise , Gautier Mathieu , Boitard Simon 
Published: February 2024

AbstractPredicting the risk of establishment and spread of populations outside their native range represents a major challenge in evolutionary biology. Various methods have recently been developed to estimate population (mal)adaptation to a new environment with genomic data via so-called Genomic Offset (GO) statistics. These approaches are particularly promising for studying invasive species, but have still rarely been used in this context. Here, we evaluated the relationship between GO and the estab-lishment probability of a population in a new environment using both in silico and empirical data. First, we designed invasion simulations to evaluate the ability to predict establishment probability of two GO computation methods (Geometric GO and Gradient Forest) under several conditions. Additionally, we aimed to evaluate the interpretability of absolute Geometric GO values, which the-oretically represent the adaptive genetic distance between populations from distinct environments. Second, utilizing public real data from the crop pest speciesBactrocera tryoni, a fruit fly native from Northern Australia, we computed GO between “source” populations and a diverse range of locations within invaded areas. This practical application of GO within the context of a biological invasion underscores its potential in providing insights and guiding recommendations for future invasion risk assessment. Overall, our results suggest that GO statistics represent good predictors of the estab-lishment probability and may thus inform invasion risk, although the influence of several factors on prediction performance (e.g. propagule pressure or admixture) will need further investigation.
The Rift Valley fever (RVF) vaccine candidate 40Fp8 shows an extreme attenuation in IFNARKO mice following intranasal inoculation
Authors: Borrego Belén , Alonso Celia , Moreno Sandra , de la Losa Nuria , Sánchez-Cordón Pedro J. , Brun Alejandro 
Published: February 2024

AbstractRift Valley fever (RVF) is an important zoonotic viral disease affecting several species of domestic and wild ruminants, causing major economic losses and dozens of human deaths in various geographical areas of Africa, where it is endemic. Although it is not present in Europe, there is a risk of its introduction and spread linked to globalisation and climate change. At present, the only measure that could help to prevent the disease is vaccination of flocks in areas at risk of RVF. Available live attenuated vaccines are an effective means of controlling the disease, but their use is often questioned due to residual virulence, particularly in susceptible hosts such as pregnant sheep. On the other hand, no vaccine is currently licensed for use in humans. The development of safe and effective vaccines is therefore a major area of research.In previous studies, we selected under selective mutagenic pressure a highly attenuated RVFV 56/74 virus variant called 40Fp8. This virus showed an extremely attenuated phenotype in both wild-type and immunodeficient A129 (IFNARKO) mice, yet was still able to induce protective immunity after a single inoculation, thus supporting its use as a safe, live attenuated vaccine. To further investigate its safety, in this work we have analysed the attenuation level of 40Fp8 in immunosuppressed mice (A129) when administered by the intranasal route, and compared it with other attenuated RVF viruses that are the basis of vaccines in use or in development. Our results show that 40Fp8 has a much higher attenuated level than these other viruses and confirm its potential as a candidate for safe RVF vaccine development.Author SummaryVaccines that use attenuated viruses are highly effective in terms of providing protection, duration, breadth, and quality of the immune response. However, they may pose a risk to immunosuppressed individuals or in certain situations, such as during pregnancy. It is therefore important to analyze the residual virulence of attenuated vaccines to ensure their safety. In this work, we analysed the safety of the RVF virus vaccine variant 40Fp8 developed in our laboratory. We studied its effect on immunodeficient mice and used a more aggressive route of administration such as the intranasal delivery route. To assess the degree of attenuation of 40Fp8, we compared it with other attenuated prototype RVF vaccines. The results clearly demonstrate that 40Fp8 is highly attenuated, and its residual virulence level is extremely low compared to other vaccine viruses tested.
Systematic mapping of MCU-mediated mitochondrial calcium signaling networks
Authors: Herran Hilda Delgado de la , Reane Denis Vecellio , Cheng Yiming , Katona Máté , Hosp Fabian , Greotti Elisa , Wettmarshausen Jennifer , Patron Maria , Mohr Hermine , Mello Natalia Prudente de , Chudenkova Margarita , Gorza Matteo , Walia Safal , Feng Michael Sheng-Fu , Leimpek Anja , Mielenz Dirk , Pellegata Natalia S. , Langer Thomas , Hajnóczky György , Mann Matthias , Murgia Marta , Perocchi Fabiana 
Published: February 2024

ABSTRACTThe Mitochondrial Ca2+Uniporter Channel (MCUC) allows calcium entry into the mitochondrial matrix to regulate energy metabolism but also cell death. Although, several MCUC components have been identified, the molecular basis of mitochondrial Ca2+signaling networks and their remodeling upon changes in uniporter activity have not been systematically assessed. Using an unbiased and quantitative proteomic approach, we map the MCUC interactome in HEK293 cells under physiological conditions and upon chronic loss or gain of mitochondrial Ca2+uptake. Besides all previously known subunits of the uniporter, we identify 89 high-confidence interactors linking MCUC to several mitochondrial complexes and pathways, half of which are currently linked to metabolic, neurological, and immunological diseases. As a proof-of-concept, we validate EFHD1 as a binding partner of MCU, EMRE and MCUB with a MICU1-dependent inhibitory effect on Ca2+uptake. To investigate compensatory mechanisms and functional consequences of mitochondrial Ca2+dyshomeostasis, we systematically survey the MCU interactome upon silencing of EMRE, MCUB, MICU1 or MICU2. We observe profound changes in the MCU interconnectivity, whereby downregulation of EMRE reduces the number of MCU interactors of over 10-fold, while silencing of MCUB leads to a wider functional network linking MCU to mitochondrial stress response pathways and cell death. Altogether our study provides a comprehensive map of MCUC protein-protein interactions and a rich, high-confidence resource that can be explored to gain insights into the players and mechanisms involved in calcium signal transduction cascades and their relevance in human diseases.
De Novo Sensorimotor Learning Through Reuse of Movement Components
Authors: Gabriel G. A. , Mushtaq F. , Morehead J. R. 
Published: February 2024

AbstractFrom tying one’s shoelaces to driving a car, complex skills involving the coordination of multiple muscles are common in everyday life; yet relatively little is known about how these skills are learned. Recent studies have shown that new sensorimotor skills involving re-mapping familiar body movements to unfamiliar outputs cannot be learned by adjusting pre-existing controllers, and that new task-specific controllers must instead be learned “de novo”. To date, however, few studies have investigated de novo learning in scenarios requiring continuous and coordinated control of relatively unpractised body movements. In this study, we used a myoelectric interface to investigate how a novel controller is learned when the task involves an unpractised combination of relatively untrained continuous muscle contractions. Over five sessions on five consecutive days, participants learned to trace a series of trajectories using a computer cursor controlled by the activation of two muscles. The timing of the generated cursor trajectory and its shape relative to the target improved for conditions trained with post-trial visual feedback. Improvements in timing transferred to all untrained conditions, but improvements in shape transferred only to untrained conditions requiring the trained order of muscle activation. All muscle outputs in the final session could already be generated during the first session, suggesting that participants learned the new task by improving the selection of existing motor commands. These results show that generating novel motor behaviours need not involve learning to generate new motor commands.Significance StatementReal-world skills often involve continuous coordination of multiple muscles. Such skills cannot be learned by adjusting an existing control policy, instead requiring a new controller to be learned “de novo”. It remains unclear how new controllers are learned for tasks involving unfamiliar combinations of body movements. In this study, we used a novel human-computer interface task to test this. Over five sessions, participants learned to trace a series of cursor trajectories by coordinating the activation of two muscles. We found that participants tended to reuse the same muscle contractions for trained and untrained variants of the task, and that performance improvements were attributable to improvements in the choice of muscle contractions from a pre-existing repertoire. Our results demonstrate that learning of new complex movements does not necessarily require learning to generate new patterns of muscle activity.
The moon’s influence on the activity of tropical forest mammals
Authors: Bischof Richard , Vallejo-Vargas Andrea F. , Semper-Pascual Asunción , Schowanek Simon D. , Beaudrot Lydia , Turek Daniel , Jansen Patrick A. , Rovero Francesco , Johnson Steig E. , Lima Marcela Guimarães Moreira , Santos Fernanda , Uzabaho Eustrate , Espinosa Santiago , Ahumada Jorge A. , Bitariho Robert , Salvador Julia , Mugerwa Badru , Sainge Moses N. , Sheil Douglas 
Published: February 2024

AbstractChanges in lunar illumination alter the balance of risks and opportunities for animals at night, influencing activity patterns and species interactions. Our knowledge about behavioral responses to moonlight is incomplete, yet it can serve to assess and predict how species respond to environmental changes such as light pollution or loss of canopy cover. As a baseline, we wish to examine if and how wildlife responds to the lunar cycle in some of the darkest places inhabited by terrestrial mammals: the floors of tropical forests.We quantified the prevalence and direction of activity responses to the moon in tropical forest mammal communities. Using custom Bayesian multinomial logistic regression models, we analyzed long-term camera trapping data on 88 mammal species from 17 protected forests on three continents. We also tested the hypothesis that nocturnal species are more prone to avoiding moonlight, as well as quantified diel activity shifts in response to moonlight.We found that, apparent avoidance of moonlight (lunar phobia, 16% of species) is more common than apparent attraction (lunar philia, 3% of species). The three species exhibiting lunar philia followed diurnal or diurnal-crepuscular activity patterns. Lunar phobia, detected in 14 species, is more pronounced with higher degree of nocturnality, and is disproportionately common among rodents. Strongly lunar phobic species were less active during moonlit nights, which in most cases also decreases their total daily activity.Our findings indicate that moonlight influences animal behavior even beneath the forest canopy. This suggests that such impacts may be exacerbated in degraded and fragmented forests. Additionally, the effect of artificial light on wild communities is becoming increasingly apparent. Our study offers empirical data from protected tropical forests as a baseline for comparison with more disturbed areas, together with a robust approach for detecting activity shifts in response to environmental change.Open Research statement:The data and code for performing the analyses described in this article are available athttps://github.com/richbi/TropicalMoon.