bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reticulate leaf venation inPilea peperomioidesis a Voronoi diagram
Authors: Zheng Xingyu , Venezia Matthew , Blum Elijah , Pedmale Ullas V. , Jackson Dave , Prusinkiewicz Przemyslaw , Navlakha Saket 
Published: July 2024

AbstractReticulate leaf venation, characterized by the presence of loops, is a distinguishing feature of many flowering plants. However, our understanding of both the geometry and the morphogenesis of reticulate vein patterns is far from complete. We show that in the Chinese money plant (Pilea peperomioides), major veins form an approximate Voronoi diagram surrounding secretory pores known as hydathodes. We also propose a mechanistic model based on polar transport of the plant hormone auxin to produce Voronoi patterns. In contrast with classical models where veins directly connect auxin sources to sinks, our model generates veins that bisect the space between adjacent auxin sources, collectively forming loops. The paradigm change offered by this model may open the door to study reticulate vein formation in other species.
Rhythmic modulation of subthalamo-pallidal interactions depends on synaptic rewiring through inhibitory plasticity
Authors: Asl Mojtaba Madadi , Lea-Carnall Caroline A. 
Published: July 2024

AbstractRhythmic stimulation offers a paradigm to modulate brain oscillations and, therefore, influence brain function. A growing body of evidence indicates that reciprocal interactions between the neurons of the subthalamic nucleus (STN) and globus pallidus externus (GPe) play a central role in the emergence of abnormal synchronous beta (15-30 Hz) oscillations in Parkinson’s disease (PD). The proliferation of inhibitory GPe-to-STN synapses following dopamine loss exacerbates this pathological activity. Rhythmic modulation of the STN and/or GPe, for example, by deep brain stimulation (DBS), can restore physiological patterns of activity and connectivity. Here, we tested whether dual targeting of STN-GPe by rhythmic stimulation can modulate pathologically strong GPe-to-STN synapses through inhibitory spike-timing-dependent plasticity (iSTDP). More specifically, we examined how time-shifted paired stimuli delivered to the STN and GPe can lead to inter-population synaptic rewiring. To that end, we first theoretically analysed the optimal range of stimulation time shift and frequency for effective synaptic rewiring. Then, as a minimal model for generating subthalamo-pallidal oscillations in healthy and PD conditions, we considered a biologically inspired STN-GPe loop comprised of conductance-based spiking neurons. Consistent with the theoretical predictions, rhythmic stimulation with appropriate time shift and frequency modified GPe-to-STN interactions through iSTDP, i.e., by long-lasting rewiring of pathologically strong synaptic connectivity. This ultimately caused desynchronising after-effects within each population such that excessively synchronous beta activity in the PD state was suppressed, resulting in a decoupling of the STN-GPe network and restoration of healthy dynamics in the model. Decoupling effects of the dual STN-GPe stimulation can be realised by time-shifted continuous and intermittent stimuli, as well as monopolar and bipolar simulation waveforms. Our findings demonstrate the critical role of neuroplasticity in shaping long-lasting stimulation effects and may contribute to the optimisation of a variety of multi-site stimulation paradigms aimed at reshaping dysfunctional brain networks by targeting plasticity.
A Drug-Elicitable Alternative-Splicing Module (DreAM) for Tunable AAV Expression and Controlled Myocardial Regeneration
Authors: Chen Zhan , Yang Luzi , Zhang Yueyang , Li Yue , Chen Gonglie , Wang Ze , Li Jiting , Yang Yuhan , Zhao Dongyu , Pu William T , Yang Ke , Dong Erdan , Guo Yuxuan 
Published: July 2024

AbstractAdeno-associated virus (AAV) is a major vector for gene therapy. A technique to fine-tune the time and level of AAV expression is lacking, which greatly restricts indication choice, therapeutic efficacy and safety. To solve this problem, here we developed a drug-elicitable alternative-splicing module (DreAM) responsive to risdiplam, an FDA-approved alternative splicing modulator. Risdiplam activates DreAM-regulated AAV expression in a dose-dependent manner with an over 2000-fold inducible change depending on the inducer dosage and the organ of interests. With a temporally resolution of a couple of days, DreAM could repeatedly activate AAV expression, determined by the frequency and duration of risdiplam administration. As an example of DreAM-realized gene therapy, this technique was used to control AAV-based cardiac delivery of YAP5SA, a potent cardiomyocyte regeneration factor. DreAM transiently activated AAV-YAP5SA, establishing the dedifferentiation-proliferation-redifferentiation cycle in cardiomyocytes. Consequently, DreAM fulfilled the regenerative capacity of AAV-YAP5SAin myocardial infarction while circumventing toxicity associated with prolonged AAV-YAP5SAexpression. Together, these data demonstrated a tremendous potential of DreAM to enhance the efficacy, safety and applicable scope of gene therapy.
HIV Coreceptors Related Genes (CCR5 and CXCR4) Promoter Methylation: Original Research
Authors: Esman Anna , Salamaikina Svetlana , Kirichenko Alina , Vinokurov Michael , Fomina Darya , Sikamov Kirill , Syrkina Arina , Pokrovskaya Anastasiya , Akimkin Vasily 
Published: July 2024

AbstractThe persistence of human immunodeficiency virus (HIV) within viral reservoirs poses significant challenges to eradication efforts. Epigenetic alterations, including DNA methylation, are potential factors influencing HIV latency and persistence. This study details the development and application of techniques to assess CpG methylation in the promoter regions of theCCR5andCXCR4genes, key HIV-1 coreceptors. Using both Sanger sequencing and pyrosequencing methods, we examined 51 biological samples from 17 HIV-1-infected individuals at three time points: baseline (Week 0) and post-antiretroviral therapy (ART) at Weeks 24 and 48. Our results revealed thatCXCR4promoter CpG sites were largely unmethylated, whileCCR5promoter CpGs exhibited significant variability in methylation levels. Specifically,CCR5CpG 1 showed a significant decrease in methylation from Week 0 to Week 48, whileCXCR4CpG 3 displayed a significant decrease between Week 0 and Week 24. These differences were statistically significant when compared with non-HIV-infected controls. These findings demonstrate distinct methylation patterns betweenCCR5andCXCR4promoters in HIV-1 positive individuals over time, suggesting that epigenetic modifications may play a role in regulating HIV-1 persistence. Our techniques provide a reliable framework for assessing gene promoter methylation and could be applied to further research in HIV epigenetics.
Intra- and interspecific variations in flight performance of oak-associated Agrilinae (Coleoptera: Buprestidae) using computerised flight mills
Authors: Le Souchu Elodie , Sallé Aurélien , Bankhead-Dronnet Stéphanie , Laparie Mathieu , Sauvard Daniel 
Published: July 2024

AbstractSeveral Agrilinae species (Coleoptera: Buprestidae) are secondary pests of broadleaf forests, and some of them are also major invasive pests. These thermophilous borers are expected to be favoured by climate change and the global deterioration of forest health, and ultimately expand their range and damage. Flight behaviour and performance of these insects are poorly known despite their critical role in dispersal inside and outside native ranges and their relevance for management purposes. This study aimed to assess intra- and interspecific variability in active flight of several Agrilinae species and effects of sex and mass on this variability to contribute to filling this gap. We assessed the flight performance of eleven species associated with oaks (nineAgrilus, oneCoraebusand oneMeliboeus) plus oneAgrilusspecies associated with the herbaceous layer. Computer-monitored flight mills were used to measure flight parameters, including periods, durations, distances and velocity in 250 beetles. Overall, flight capacities were rather homogeneous among species, with a dominance of poor flyers and onlyCoraebus undatusshowed outstanding performance. Beetles generally performed several short flight bouts within one trial, and only a few individuals sustained long flight. The maximal total distance covered across multiple assays until death ranged from 170 to 16 097 m depending on the species, with a median between 35 and 966 m (excluding individuals that never flew). On top of this interspecific variability, flight distances also varied greatly among individuals, but were not influenced by sex. Preflight body mass had mixed effects depending on the species, presumably related to different dispersal patterns. In our experimental conditions, most species had limited average dispersal capacities over multiple flight trials. Overall, dispersal over long distances and colonisation events probably depend mainly on a small proportion of individuals which largely exceeded the median performance.
Genomic prediction of heterosis, inbreeding control, and mate allocation in outbred diploid and tetraploid populations
Authors: Endelman Jeffrey B. 
Published: July 2024

AbstractBreeders have long appreciated the need to balance selection for short-term genetic gain with maintaining genetic variance for long-term gain. For outbred populations, the method called Optimum Contribution Selection (OCS) chooses parental contributions to maximize the average breeding value at a prescribed inbreeding rate. With Optimum Mate Allocation (OMA), the contribution of each mating is optimized, which allows for specific combining ability due to dominance. To enable OCS and OMA in polyploid species, new theoretical results were derived to (1) predict mid-parent heterosis due to dominance and (2) control inbreeding in a population of arbitrary ploidy. A new Convex optimization framework for OMA, named COMA, was developed and released as public software. Under stochastic simulation of a genomic selection program, COMA maintained a target inbreeding rate of 0.5% using either pedigree or genomic IBD kinship. Significantly more genetic gain was realized with pedigree kinship, which is consistent with previous studies showing the selective advantage of an individual under OCS is dominated by its Mendelian sampling term. Despite the higher accuracy (+0.2–0.3) when predicting mate performance with OMA compared to OCS, there was little long-term gain advantage. The sparsity of the COMA mating design and flexibility to incorporate mating constraints offer practical incentives over OCS. In a potato breeding case study with 170 candidates, the optimal solution at 0.5% inbreeding involved 43 parents but only 43 of the 903 possible matings.
Pollinators differentially respond to local and landscape grassland features
Authors: Lichtenberg Elinor M. , Heiser Jaclyn , Baum Kristen A. , Neff John L. , Jha Shalene 
Published: July 2024

AbstractPredicting how habitat composition alters communities of mobile ecosystem service providers remains a major challenge in community ecology. This is partially because separate taxonomic groups that provide the same service may respond uniquely to changes in habitat and associated resource availability. Further, the spatial scale at which habitat features impact each group can vary. Failure to account for these differences significantly limits the ability to quantify shared versus contrasting responses to habitat for important ecosystem service-providing groups.We investigated the impacts of local (habitat patch level) and landscape features in the US Southern Great Plains on groups of pollinating insects with different basic biologies: Coleoptera, Diptera, Hymenoptera, and Lepidoptera. Habitat features included local flower and shelter resources as well as landscape-scale semi-natural habitat.We found that bare ground supported more Hymenoptera and Lepidoptera but fewer Diptera, while more diverse flower communities supported more Hymenoptera but fewer Coleoptera. Interestingly, given that this study occurred in a grassland system, forest cover in the surrounding landscape more strongly affected pollinator diversity than grassland cover did. Landscapes with more woodland had higher Coleoptera and Diptera richness.Our results highlight that pollinator conservation and sustainable land management depend on understanding the habitat needs, including shelter, of diverse pollinators. Because taxa can have opposite responses to specific habitat features or scales, providing a range of grassland management practices (e.g., variety in the timing and type of biomass removal) may be the most effective approach to support the broader pollinator community.
The CCT chaperonin and actin modulate the ER and RNA-binding protein condensation during oogenesis to maintain translational repression of maternal mRNA and oocyte quality
Authors: Elaswad Mohamed T. , Gao Mingze , Tice Victoria E. , Bright Cora G. , Thomas Grace M. , Munderloh Chloe , Trombley Nicholas J. , Haddad Christya N. , Johnson Ulysses G. , Cichon Ashley N. , Schisa Jennifer A. 
Published: July 2024

AbstractThe regulation of maternal mRNAs is essential for proper oogenesis, the production of viable gametes, and to avoid birth defects and infertility. Many oogenic RNA-binding proteins have been identified with roles in mRNA metabolism, some of which localize to dynamic ribonucleoprotein granules and others that appear dispersed. Here, we use a combination ofin vitrocondensation assays and thein vivo C. elegansoogenesis model to determine the intrinsic properties of the conserved KH-domain MEX-3 protein and to identify novel regulators of MEX-3 and the Lsm protein, CAR-1. We demonstrate that MEX-3 undergoes liquid-liquid phase separation and appears to have intrinsic gel-like propertiesin vitro. We also identify novel roles for the CCT chaperonin and actin in preventing ectopic RNA-binding protein condensates in maturing oocytes that appear to be independent of MEX-3 folding. CCT and actin also oppose the expansion of ER sheets that may promote ectopic condensation of RNA-binding proteins that are associated with de-repression of maternal mRNA. This regulatory network is essential to preserve oocyte quality, prevent infertility, and may have implications for understanding the role of hMex3 phase transitions in cancer.Significance statement:The molecular mechanisms that regulate phase transitions of oogenic RNA-binding proteins are critical to elucidate but are not fully understood.We identify novel regulators of RNA-binding protein phase transitions in maturing oocytes that are required to maintain translational repression of maternal mRNAs and oocyte quality.This study is the first to elucidate a regulatory network involving the CCT chaperonin, actin, and the ER for phase transitions of RNA-binding proteins during oogenesis. Our findings for the conserved MEX-3 protein may also be applicable to better understanding the role of hMex3 phase transitions in cancer.
BaCoN (Balanced Correlation Network) improves prediction of gene buffering
Authors: Rohde Thomas , Demirtas Talip Yasir , Shaw Angela Helen , Billmann Maximilian 
Published: July 2024

ABSTRACTBuffering between genes is fundamental for robust cellular functions. While experimentally testing all possible gene pairs is infeasible, gene buffering can be predicted genome-wide under the assumption that a gene’s buffering capacity depends on its expression level and the absence of this buffering capacity primes a severe fitness phenotype of the buffered gene. We developed BaCoN (BalancedCorrelationNetwork), a post-hoc unsupervised correction method that amplifies specific signals in expression-vs-fitness effect correlation-based networks. We quantified 147 million potential buffering relationships by associating CRISPR-Cas9-screening fitness effects with transcriptomic data across 1019 Cancer Dependency Map (DepMap) cell lines. BaCoN outperformed state-of-the-art methods including multiple linear regression, based on our newly compiled metrics for gene buffering predictions. Combining BaCoN with batch correction or Cholesky data whitening further boosts predictive performance. We characterized a high-confidence list of 899 buffering predictions and found that while buffering genes overall are often syntenic, buffering paralogs are on different chromosomes. BaCoN performance increases with more screens and genes considered, making it a valuable tool for gene buffering predictions from the constantly growing DepMap.
Distinct populations suppress or escalate intake of cocaine paired with aversive quinine
Authors: Powers Rosalie E. , Fogel Peter A. , Reeves Jayson H. , Madrid Pamela , Moschak Travis M. 
Published: July 2024

AbstractBackgroundOnly a subset of individuals who encounter drugs of abuse become habitual users. Aversive subjective effects like coughing and unpleasant taste are predictors for continued use. While several preclinical studies have explored self-administration involving aversive cues, none have simultaneously introduced aversion with the initial drug self-administration. We aimed to develop a clinically relevant model by pairing intravenous cocaine with intraoral quinine self-administration from the outset and investigating whether repeated exposure to an aversive stimulus would alter its hedonic value under laboratory conditions.MethodsTwenty-seven male and female Sprague Dawley rats self-administered intravenous/intraoral (cocaine/quinine) for 2 hr/day over 14 days. This was followed by a 1-day quinine-only extinction session, a 3-day return to self-administration, and an intraoral infusion session to assess quinine taste reactivity (TR).ResultsWe identified three distinct groups. The first self-administered very little cocaine, while the second sharply escalated cocaine intake. Both groups had similar aversive TR to quinine, suggesting that the escalating group did not habituate to the aversive cue but pursued drug despite it. We also identified a third group with high initial intake that decreased over time. This decrease predicted high aversive TR, and we argue this group may represent individuals who “overindulge” on their first use and subsequently find self-administration to be aversive.ConclusionsOur novel model mimics real-world variability in initial interactions with drugs of abuse and yields three distinct groups that differ in self-administration patterns and aversive cue valuation.
Vasopressin-to-Oxytocin Receptor Crosstalk in the Preoptic Area Underlying Parental Behaviors in Male Mice
Authors: Inada Kengo , Hagihara Mitsue , Yaguchi Kasane , Irie Satsuki , Inoue Yukiko U. , Inoue Takayoshi , Miyamichi Kazunari 
Published: July 2024

AbstractThe transition to parenthood brings significant changes in behavior toward offspring. For instance, in anticipation of their offspring, male mice shift from infanticidal to caregiving behaviors. While the release of oxytocin from the paraventricular hypothalamus (PVH) plays a critical role in paternal caregiving, it does not fully account for the entire behavioral shift. The specific downstream neurons and signaling mechanisms involved in this process remain obscure. Here, we demonstrate that PVH vasopressin neurons also essentially contribute to a paternal behavioral shift. This vasopressin signal is partially transmitted through oxytocin receptors (OTRs) expressed in the anterior commissure and medial nuclei of the preoptic area. These OTR-expressing neurons receive inputs from both PVH oxytocin and vasopressin neurons and are responsible for expressing paternal caregiving behaviors. Collectively, this non-canonical vasopressin-to-OTR crosstalk within specific limbic circuits acts as a pivotal regulator of paternal behavioral changes in mice.HighlightsPVH vasopressin neurons are required for and can trigger paternal caregiving behaviors.Vasopressin-induced paternal behaviors are mediated in part by OTRs in the preoptic area (POA).POA OTR neurons receive inputs from both PVH oxytocin and vasopressin neurons.POA OTR neurons play a critical and facilitative role in promoting paternal caregiving behaviors.
Structural basis of the human transcriptional Mediator complex modulated by its dissociable Kinase module
Authors: Chen Shin-Fu , Chao Ti-Chun , Kim Hee Jong , Tang Hui-Chi , Khadka Subash , Li Tao , Lee Dung-Fang , Murakami Kenji , Boyer Thomas G. , Tsai Kuang-Lei 
Published: July 2024

SummaryThe eukaryotic Mediator, comprising a large Core (cMED) and a dissociable CDK8 kinase module (CKM), regulates RNA Polymerase II (Pol II)-dependent transcription. cMED recruits Pol II and promotes pre-initiation complex (PIC) formation in a manner inhibited by the CKM, which is also implicated in post-initiation control of gene expression. Herein we report cryo-electron microscopy structures of the human complete Mediator and its CKM, which explains the basis for CKM inhibition of cMED-activated transcription. The CKM binds to cMED through an intrinsically disordered region (IDR) in MED13 and HEAT repeats in MED12. The CKM inhibits transcription by allocating its MED13 IDR to occlude binding of Pol II and MED26 to cMED and further obstructing cMED-PIC assembly through steric hindrance with TFIIH and the +1 nucleosome. Notably, MED12 binds to the cMED Hook, positioning CDK8 downstream of the transcription start site, which sheds new light on its stimulatory function in post-initiation events.
Preclinical evaluation of pharmacological inhibition of SIRT1 on the growth of tumoral and metastatic granulosa cells
Authors: Cluzet Victoria , Airaud Eloïse , Devillers Marie M , Petit Florence , Leary Alexandra , Pierre Alice , Li Haojian , Day Chi-Ping , Weyemi Urbain , Chauvin Stéphanie , Guigon Céline J 
Published: July 2024

AbstractBackgroundClinical management of patients with recurrent ovarian granulosa cell tumor (GCT) remains poor. Sirtuin-1 (SIRT1), a deacetylase enzyme involved in the regulation of tumor growth and metastasis, may represent a therapeutic target due to the availability of selective pharmacological inhibitors with minimal toxicity.MethodsWe assessed the possible overexpression of SIRT1 during tumorigenesis by Western blot and immunohistochemistry. We tested the effects of SIRT1 inhibition by EX-527 on growth, proliferation, death, migration and gene expression by RNA sequencing and RT-qPCRin vitroon three GCT cell lines (AT29, KGN, COV434). Tumor growth in response to EX-527 treatment was examined in nude mice carrying subcutaneous GCT cell grafts using an electronic caliper and in GCT of AT83 mice by 3D ultrasound imaging system.ResultsSIRT1 abundance increased during tumorigenesis.In vitrotreatment with EX-527 efficiently reduced cell growth, either by inducing apoptosis or by inhibiting proliferation. EX-527 induced alterations in pathways driven by mTOR, Myc and E2F, and in pathways controlling cell metabolism and oxidative stress. The administration of this treatment for 4 weeks efficiently reduced tumor progressionin vivo.ConclusionsOur study reveals a new therapeutic potential of SIRT1 targeting as a treatment option for patients with recurrent GCT.