bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cooperation between Caenorhabditis elegansCOMPASS and condensin in germline chromatin organization
Authors: Herbette M. , Robert V. , Bailly A. , Gely L. , Feil R. , Llères D. , Palladino F. 
Published: May 2020

AbstractDeposition of histone H3 lysine 4 (H3K4) methylation at promoters by SET1/COMPASS is associated with context-dependent effects on gene expression and local changes in chromatin organization. Whether SET1/COMPASS also contributes to higher-order chromosome structure has not been investigated. Here, we address this question by quantitative FRET (Förster resonance energy transfer)-based fluorescence lifetime imaging microscopy (FLIM) onC. elegansgerm cells expressing histones H2B-eGFP and H2B-mCherry. We find that SET1/COMPASS subunits strongly influence meiotic chromosome organization, with marked effects on the close proximity between nucleosomes. We further show that inactivation of SET-2, theC. eleganshomologue of SET1, or CFP-1, the chromatin targeting subunit of COMPASS, strongly enhance chromosome organization defects and loss of fertility resulting from depletion of condensin-II. Defects in chromosome morphology resulting from conditional inactivation of topoisomerase II, another structural component of chromosomes, were also aggravated in the absence of SET-2. Combined, ourin vivofindings suggest a model in which the SET1/COMPASS histone methyltransferase complex plays a role in shaping meiotic chromosome in cooperation with the non-histone proteins condensin-II and topoisomerase.
Cortex cis-regulatory switches establish scale colour identity and pattern diversity inHeliconius
Authors: Livraghi Luca , Hanly Joseph J. , Van Belleghem Steven M. , Montejo-Kovacevich Gabriela , van der Heijden Eva S. M. , Loh Ling Sheng , Ren Anna , Warren Ian A. , Lewis James J. , Concha Carolina , López Laura H. , Wright Charlotte , Walker Jonah M. , Foley Jessica , Goldberg Zachary H. , Arenas-Castro Henry , Perry Michael W. , Papa Riccardo , Martin Arnaud , McMillan W. Owen , Jiggins Chris D. 
Published: May 2020

AbstractInHeliconiusbutterflies, wing pattern diversity is controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation. One of these genes,cortex, has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knock-outs in multipleHeliconiusspecies and show thatcortexis a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identifiedcis-regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In theH. melpomene/timaretalineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting thatcis-regulatory structural variation underlies these mimetic adaptations. Our work shows thatcortexfunctionally controls scale colour fate and that itscis-regulatory regions control a phenotypic switch in a modular and pattern-specific fashion.
An efficient gene excision system in maize
Authors: Wang Ning , Arling Maren , Hoerster George , Ryan Larisa , Wu Emily , Lowe Keith , Gordon-Kamm Bill , Jones Todd J. , Chilcoat Nicholas Doane , Anand Ajith 
Published: May 2020

ABSTRACTUse of the morphogenic genesBaby Boom(Bbm) andWuschel2(Wus2), along with new ternary constructs, has increased the genotype range and the type of explants that can be used for maize transformation. In addition, altering the ectopic expression pattern forBbm/Wus2has resulted in rapid maize transformation methods that are faster and applicable to a broader range of inbreds. However, expression ofBbm/Wus2can compromise the quality of regenerated plants, leading to sterility. We reasoned excising morphogenic genes after transformation but before regeneration would increase production of fertile T0 plants. We developed a method that uses an inducible site-specific recombinase (Cre) to excise morphogenic genes. The use of developmentally regulated promoters, such asOle, Glb1, End2andLtp2, to driveCreenabled excision of morphogenic genes in early embryo development and produced excised events at a rate of 25%-100%. A different strategy utilizing an excision-activated selectable marker produced excised events at a rate of 53.3%-68.4%; however, the transformation frequency was lower (12.9%-49.9%). The use of inducible heat shock promoters (e.g.Hsp17.7, Hsp26) to express Cre, along with improvements in tissue culture conditions and construct design, resulted in high frequencies of T0 transformation (29%-69%), excision (50%-97%), usable quality events (3.6%-14%), and few escapes (non-transgenic; 14%-17%) in three elite maize inbreds. Transgenic events produced by this method are free of morphogenic and marker genes.
Robot-aided Training of Propulsion During Walking: Effects of Torque Pulses Applied to the Hip and Knee Joints During Stance
Authors: McGrath Robert , Bodt Barry , Sergi Fabrizio 
Published: May 2020

AbstractThe goal of this study is to evaluate the effects of the application of torque pulses to the hip and knee joint via a robotic exoskeleton in the context of training propulsion during walking. Based on our previous biomechanical study, we formulated a set of conditions of torque pulses applied to the hip and knee joint associated with changes in push-off posture, a component of propulsion. In this work, we quantified the effects of hip/knee torque pulses on metrics of propulsion, specifically hip extension (HE) and normalized propulsive impulse (NPI), in two experiments. In the first experiment, we exposed 16 participants to sixteen conditions of torque pulses during single strides to observe the immediate effects of pulse application. In the second experiment, we exposed 16 participants to a subset of those conditions to observe short-term adaptation effects.During pulse application, NPI aligned with the expected modulation of push-off posture, while HE was modulated in the opposite direction. The timing of the applied pulses, early or late stance, was crucial, as the effects were often in the opposite direction when changing timing condition. Extension torque applied at late stance increased HE in both experiments range of change in HE: (1.6 ± 0.3 deg, 7.7 ± 0.9 deg),p< 0.001). The same conditions resulted in a negative change in NPI only in the single pulse experiment — change in NPI for knee torque: −2.9 ± 0.3 ms,p< 0.001, no significant change for hip torque. Also, knee extension and flexion torque during early and late stance, respectively, increased NPI during single pulse application — range of change in NPI: (3.4, 4.2) ± 0.3 ms,p< 0.001). During repeated pulse application, NPI increased for late stance flexion torque — range of change in NPI: (4.5, 4.8) ± 2 ms,p< 0.001), but not late stance extension torque. Upon pulse torque removal, we observed positive after-effects in HE in all conditions. While there were no after-effects in NPI significant at the group level, a responder analysis indicated that the majority of the group increased both NPI and HE after pulse application.
Physiological and molecular responses to combinatorial iron and phosphate deficiencies in hexaploid wheat seedlings
Authors: Kaur Gazaldeep , Shukla Vishnu , Meena Varsha , Kumar Anil , Tyagi Deepshikha , Singh Jagtar , Kandoth Pramod Kaitheri , Mantri Shrikant , Rouached Hatem , Pandey Ajay Kumar 
Published: May 2020

ABSTRACTIron (Fe) and phosphorus (P) are the essential mineral nutrient for plant growth and development. However, the molecular interaction of the Fe and P pathways in crops remained largely obscure. In this study, we provide a comprehensive physiological and molecular analysis of hexaploid wheat response to single (Fe, P) and its combinatorial deficiencies. Our data showed that inhibition of the primary root growth occurs in response to Fe deficiency; however, growth was rescued when combinatorial deficiencies occurred. Analysis of RNAseq revealed that distinct molecular rearrangements during combined deficiencies with predominance for genes related to metabolic pathways and secondary metabolite biosynthesis primarily include genes for UDP-glycosyltransferase, cytochrome-P450s, and glutathione metabolism. Interestingly, the Fe-responsive cis-regulatory elements in the roots in Fe stress conditions were enriched compared to the combined stress. Our metabolome data also revealed the accumulation of distinct metabolites such as amino-isobutyric acid, arabinonic acid, and aconitic acid in the combined stress environment. Overall, these results are essential in developing new strategies to improve the resilience of crops in limited nutrients.HIGHLIGHTSThis study was performed to understand the molecular changes occurring during the interaction of Phosphorus (P) and Iron (Fe) in hexaploid wheat roots.P and Fe show cross-talk as Fe deficiency-induced phenotype that was restored by the withdrawal of P.A total of 2780 differentially expressed genes were identified in the roots with the combined –Fe–P deficiencies with predominance for UDP-glycosyltransferases, cytochrome-450 and glutathione-S-transferases transcripts.The metabolomic changes identified the importance of amino-isobutyric acid, arabinonic acid and aconitic acid during dual deficiencyThis work provides a comprehensive insight to understand the molecular rearrangements occurring in wheat roots during Fe and P interaction.
Injectable hydrogels for sustained co-delivery of subunit vaccines enhance humoral immunity
Authors: Roth Gillie A. , Gale Emily C. , Alcántara-Hernández Marcela , Luo Wei , Axpe Eneko , Verma Rohit , Yin Qian , Yu Anthony C. , Hernandez Hector Lopez , Maikawa Caitlin L. , Smith Anton A. A. , Davis Mark M. , Pulendran Bali , Idoyaga Juliana , Appel Eric A. 
Published: May 2020

AbstractVaccines aim to elicit a robust, yet targeted, immune response. Failure of a vaccine to elicit such a response arises in part from inappropriate temporal control over antigen and adjuvant presentation to the immune system. In this work, we sought to exploit the immune system’s natural response to extended pathogen exposure during infection by designing an easily administered slow-delivery vaccine platform. We utilized an injectable and self-healing polymer-nanoparticle (PNP) hydrogel platform to prolong the co-delivery of vaccine components to the immune system. We demonstrated that these hydrogels exhibit unique delivery characteristics whereby physicochemically distinct compounds (such as antigen and adjuvant) could be co-delivered over the course of weeks. When administered in mice, hydrogel-based sustained vaccine exposure enhanced the magnitude, duration, and quality of the humoral immune response compared to standard PBS bolus administration of the same model vaccine. We report that the creation of a local inflammatory niche within the hydrogel, coupled with sustained release of vaccine cargo, enhanced the magnitude and duration of germinal center responses in the lymph nodes. This strengthened germinal center response promoted greater antibody affinity maturation, resulting in a more than 1000-fold increase in antigen-specific antibody affinity in comparison to bolus immunization. In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of subunit vaccines.
Context matters: Situational stress impedes functional reorganization of intrinsic brain connectivity during problem solving
Authors: Liu Mengting , Backer Robert A. , Amey Rachel C. , Splan Eric E. , Magerman Adam , Forbes Chad E. 
Published: May 2020

AbstractExtensive research has established the relationship between individual differences in brain activity in a resting state and individual differences in behavior. Conversely, when individuals are engaged in various tasks, certain task-evoked reorganization occurs in brain functional connectivity, which consequently can influence individuals’ performance as well. Here, we show that resting state and task-dependent state brain patterns interact as a function of contexts engendering stress. Findings revealed that when the resting state connectome was examined during performance, the relationship between connectome strength and performance only remained for participants under stress (who also performed worse than all other groups on the math task), suggesting stress preserved brain patterns indicative of underperformance whereas non-stressed individuals spontaneously transitioned out of brain patterns indicative of underperformance. These findings were subsequentially replicated in an independent sample set. Implications are discussed for network dynamics as a function of context.
Model-based fMRI reveals co-existing specific and generalized concept representations
Authors: Bowman Caitlin R. , Iwashita Takako , Zeithamova Dagmar 
Published: May 2020

AbstractThere has been a long-standing debate about whether categories are represented by individual category members (exemplars) or by the central tendency abstracted from individual members (prototypes). Across neuroimaging studies, there has been neural evidence for either exemplar representations or prototype representations, but not both. In the present study, we asked whether it is possible for individuals to form multiple types of category representations within a single task. We designed a categorization task to promote both exemplar and prototype representations, and we tracked their formation across learning. We found evidence for co-existing prototype and exemplar representations in brain in regions that aligned with previous studies: prototypes in ventromedial prefrontal cortex and anterior hippocampus and exemplars in inferior frontal gyrus and lateral parietal cortex. These findings show that, under the right circumstances, individuals may form representations at multiple levels of specificity, potentially facilitating a broad range of future memory-based decisions.
Cellular-scale silicon probes for high-density, precisely-localized neurophysiology
Authors: Egert Daniel , Pettibone Jeffrey R , Lemke Stefan , Patel Paras R. , Caldwell Ciara M. , Cai Dawen , Ganguly Karunesh , Chestek Cynthia A. , Berke Joshua D. 
Published: May 2020

AbstractNeural implants with large numbers of electrodes have become an important tool for examining brain functions. However, these devices typically displace a large intracranial volume compared to the neurons they record. This large size limits the density of implants, provokes tissue reactions that degrade chronic performance, and impedes the ability to accurately visualize recording sites within intact circuits. Here we report next-generation silicon-based neural probes at cellular-scale (5×10µm cross-section), with ultra-high-density packing (as little as 66µm between shanks) and 64 or 256 closely-spaced recording sites per probe. We show that these probes can be inserted into superficial or deep brain structures and maintain high-quality spike recordings in freely behaving rats for many weeks. Finally, we demonstrate a slice-in-place approach for the precise registration of recording sites relative to nearby neurons and anatomical features, including striatal µ-opioid receptor patches. This scalable technology provides a valuable tool for examining information processing within neural circuits, and potentially for human brain-machine interfaces.
Sick of Eating: eco-evo-immuno dynamics of predators and their trophically acquired parasites
Authors: Fleischer Samuel R. , Bolnick Daniel I. , Schreiber Sebastian J. 
Published: May 2020

AbstractWhen predators consume prey, they risk becoming infected with their prey’s parasites, which can then establish the predator as a secondary host. For example, stickleback in northern temperate lakes consume benthic or limnetic prey, which are intermediate hosts for distinct species of parasites (e.g.Eustrongylidesnematodes in benthic oligocheates andSchistocephalus soliduscopepods in limnetic copepods). These worms then establish the stickleback as a secondary host and can cause behavioral changes linked to increased predation by birds. In this study, we use a quantitative genetics framework to consider the simultaneous eco-evolutionary dynamics of predator ecomorphology and predator immunity when alternative prey may confer different parasite exposures. When evolutionary tradeoffs are sufficiently weak, predator ecomorphology and immunity are correclated among populations, potentially generating a negative correlation between parasite intake and infection.
Sparsely-Connected Autoencoder (SCA) for single cell RNAseq data mining
Authors: Alessandri L , Cordero F , Beccuti M , Licheri N , Arigoni M , Olivero M , Di Renzo F , Sapino A , Calogero RA 
Published: May 2020

AbstractSingle-cell RNA sequencing (scRNAseq) is an essential tool to investigate cellular heterogeneity. Although scRNAseq has some technical challenges, it would be of great interest being able to disclose biological information out of cell subpopulations, which can be defined by cluster analysis of scRNAseq data. In this manuscript, we evaluated the efficacy of sparsely-connected autoencoder (SCA) as tool for the functional mining of single cells clusters. We show that SCA can be uses as tool to uncover hidden features associated to scRNAseq data. Our approach is strengthened by two metrics, QCF and QCM, which respectively allow to evaluate the ability of SCA to reconstruct a cells cluster and to evaluate the overall quality of the neural network model. Our data indicate that SCA encoded spaces, derived by different experimentally validated data (TFs targets, miRNAs targets, Kinases targets, and cancer-related immune signatures), can be used to grasp single cell cluster-specific functional features. In our implementation, SCA efficacy comes from its ability to reconstruct only specific clusters, thus indicating only those clusters where the SCA encoding space is a key element for cells aggregation. SCA analysis is implemented as module in rCASC framework and it is supported by a GUI to simplify it usage for biologists and medical personnel.
Oncogenic mutation or overexpression of oncogenic KRAS or BRAF is not sufficient to confer oncogene addiction
Authors: Ito Reina E. , Oneyama Chitose , Aoki Kazuhiro 
Published: May 2020

AbstractOncogene addiction is a cellular property by which cancer cells become highly dependent on the expression of oncogenes for their survival. Oncogene addiction can be exploited to design molecularly targeted drugs that kill only cancer cells by inhibiting the specific oncogenes. Genes and cell lines exhibiting oncogene addiction, as well as the mechanisms by which cell death is induced when addicted oncogenes are suppressed, have been extensively studied. However, it is still not fully understood how oncogene addiction is acquired in cancer cells. Here, we take a synthetic biology approach to investigate whether oncogenic mutation or oncogene expression suffices to confer the property of oncogene addiction to cancer cells. We employed human mammary epithelium-derived MCF-10A cells expressing the oncogenic KRAS or BRAF. MCF-10A cells harboring an oncogenic mutation in a single-allele of KRAS or BRAF showed weak tumorigenic activity, but no characteristics of oncogene addiction. MCF-10A cells overexpressing oncogenic KRAS demonstrated the tumorigenic activity, but MCF-10A cells overexpressing oncogenic BRAF did not. Neither cell line exhibited any oncogene addiction properties. These results indicate that the introduction of oncogenic mutation or the overexpression of oncogenes is not sufficient for cancer cells to acquire oncogene addiction, and that oncogene addiction is not associated with tumorigenic potential.
Adolescent frontal top-down neurons receive heightened local drive to establish adult attentional behavior in mice
Authors: Nabel Elisa M , Garkun Yury , Koike Hiroyuki , Sadahiro Masato , Liang Ana , Norman Kevin J , Taccheri Giulia , Demars Michael P. , Im Susanna , Caro Keaven , Lopez Sarah , Bateh Julia , Hof Patrick R. , Clem Roger L. , Morishita Hirofumi 
Published: May 2020

AbstractFrontal top-down cortical neurons projecting to sensory cortical regions are well-positioned to integrate long-range inputs with local circuitry in frontal cortex to implement top-down attentional control of sensory regions. How adolescence contributes to the maturation of top-down neurons and associated local/long-range input balance, and the establishment of attentional control is poorly understood. Here we combine projection-specific electrophysiological and rabies-mediated input mapping in mice to uncover adolescence as a developmental stage when frontal top-down neurons projecting from the anterior cingulate to visual cortex are highly functionally integrated into local excitatory circuitry and have heightened activity compared to adulthood. Chemogenetic suppression of top-down neuron activity selectively during adolescence, but not later periods, produces long-lasting visual attentional behavior deficits, and results in excessive loss of local excitatory inputs in adulthood. Our study reveals an adolescent sensitive period when top-down neurons integrate local circuits with long-range connectivity to produce attentional behavior.
Distinct Long-term Effects of Precision X-Radiation on Reflex Saliva Flow Rate and Tissue Integrity in a Preclinical Model of Chronic Hyposalivation
Authors: Aalam Syed Mohammed Musheer , Viringipurampeer Ishaq A. , Walb Matthew C. , Tryggestad Erik J. , Emperumal Chitra P. , Song Jianning , Xu Xuewen , Saini Rajan , Lombaert Isabelle M.A. , Sarkaria Jann N. , Garcia Joaquin , Janus Jeffrey R. , Kannan Nagarajan 
Published: May 2020

AbstractChronic salivary hypofunction and xerostomia are common side effects of radiation therapy which is an essential component in the curative management in patients with head & neck cancers. Over the years, improvements in delivery techniques such as image-guided intensity modulated radiation therapy have led to improvement in cancer management but chronic hyposalivation continues to be a challenge that causes long-term health implications resulting in compromised quality of life. Recent advances in salivary stem cell research promise new frontier in the treatment of radiation-induced hyposalivation by initiating regeneration of radiation-damaged salivary parenchymal cells. Lack of a standard preclinical immunodeficient model to assess radiation-induced changes objectively and quantitatively in salivary flow rates will impede rapid progress towards the development of cellular therapies for chronic salivary dysfunction and attendant xerostomia. Herein, we report the first fully characterized novel cone-beam computed tomography (CBCT)-guided precision ionizing radiation (IR) induced chronic hyposalivation model in radiosensitive, immunodeficient transgenic NSG-SGM3 mice expressing three human cytokines including c-KIT ligand/stem cell factor. Additionally, we also report a novel and instantaneous method to objectively assess the kinetics of pilocarpine-stimulated salivary flowrate. Comprehensive structural and functional characterization of salivary glands revealed previously unknown and highly complex gender, age, IR dose and salivary gland subtype-specific effects of salivary-ablative precision IR.