bluuebunny/crossref_metadata_2025_split huggingface dataset:
A split-GAL4 driver line resource forDrosophilaneuron types
Authors: Meissner Geoffrey W , Vannan Allison , Jeter Jennifer , Close Kari , DePasquale Gina M , Dorman Zachary , Forster Kaitlyn , Beringer Jaye Anne , Gibney Theresa V , Hausenfluck Joanna H , He Yisheng , Henderson Kristin , Johnson Lauren , Johnston Rebecca M , Ihrke Gudrun , Iyer Nirmala , Lazarus Rachel , Lee Kelley , Li Hsing-Hsi , Liaw Hua-Peng , Melton Brian , Miller Scott , Motaher Reeham , Novak Alexandra , Ogundeyi Omotara , Petruncio Alyson , Price Jacquelyn , Protopapas Sophia , Tae Susana , Taylor Jennifer , Vorimo Rebecca , Yarbrough Brianna , Zeng Kevin Xiankun , Zugates Christopher T , Dionne Heather , Angstadt Claire , Ashley Kelly , Cavallaro Amanda , Dang Tam , Gonzalez Guillermo A , Hibbard Karen L , Huang Cuizhen , Kao Jui-Chun , Laverty Todd , Mercer Monti , Perez Brenda , Pitts Scarlett , Ruiz Danielle , Vallanadu Viruthika , Zheng Grace Zhiyu , Goina Cristian , Otsuna Hideo , Rokicki Konrad , Svirskas Robert R , Cheong Han SJ , Dolan Michael-John , Ehrhardt Erica , Feng Kai , Galfi Basel El , Goldammer Jens , Huston Stephen J , Hu Nan , Ito Masayoshi , McKellar Claire , Minegishi Ryo , Namiki Shigehiro , Nern Aljoscha , Schretter Catherine E , Sterne Gabriella R , Venkatasubramanian Lalanti , Wang Kaiyu , Wolff Tanya , Wu Ming , George Reed , Malkesman Oz , Aso Yoshinori , Card Gwyneth M , Dickson Barry J , Korff Wyatt , Ito Kei , Truman James W , Zlatic Marta , Rubin Gerald M ,   FlyLight Project Team
Published: January 2024

AbstractTechniques that enable precise manipulations of subsets of neurons in the fly central nervous system have greatly facilitated our understanding of the neural basis of behavior. Split-GAL4 driver lines allow specific targeting of cell types inDrosophila melanogasterand other species. We describe here a collection of 3060 lines targeting a range of cell types in the adultDrosophilacentral nervous system and 1373 lines characterized in third-instar larvae. These tools enable functional, transcriptomic, and proteomic studies based on precise anatomical targeting. NeuronBridge and other search tools relate light microscopy images of these split-GAL4 lines to connectomes reconstructed from electron microscopy images. The collections are the result of screening over 77,000 split hemidriver combinations. Previously published and new lines are included, all validated for driver expression and curated for optimal cell type specificity across diverse cell types. In addition to images and fly stocks for these well-characterized lines, we make available 300,000 new 3D images of other split-GAL4 lines.
Transcription factor dynamics, oscillation, and functions in human enteroendocrine cell differentiation
Authors: Singh Pratik N. P. , Gu Wei , Madha Shariq , Lynch Allen W. , Cejas Paloma , He Ruiyang , Bhattacharya Swarnabh , Gomez Miguel M. , Oser Matthew G. , Brown Myles , Long Henry W. , Meyer Clifford A. , Zhou Qiao , Shivdasani Ramesh A. 
Published: January 2024

SummaryEnteroendocrine cells (EECs), which secrete serotonin (enterochromaffin cells, EC) or a dominant peptide hormone, serve vital physiologic functions. As with any adult human lineage, the basis for terminal cell diversity remains obscure. We replicated human EEC differentiationin vitro, mapped transcriptional and chromatin dynamics that culminate in discrete cell types, and studied abundant EEC precursors expressing selected transcription factors (TFs) and gene programs. Before expressing the pre-terminal factor NEUROD1, non-replicating precursors oscillated between epigenetically similar but transcriptionally distinctASCL1+andHES6hicell states. Loss of either factor substantially accelerated EEC differentiation and disrupted EEC individuality; ASCL1 or NEUROD1 deficiency had opposing consequences on EC and hormone-producing cell features. Expressed late in EEC differentiation, the latter TFs mainly bindcis-elements that are accessible in undifferentiated stem cells and tailor the subsequent expression of TF combinations that specify EEC types. Thus, TF oscillations retard EEC maturation to enable accurate EEC diversification.
Definition of regulatory elements and transcription factors controlling immune cell gene expression at single cell resolution using single nucleus ATAC-seq
Authors: Yang Pengxin , Corbett Ryan , Daharsh Lance , Uribe Juber Herrera , Byrne Kristen A. , Loving Crystal L. , Tuggle Christopher 
Published: January 2024

ABSTRACTThe transcriptome of porcine peripheral blood mononuclear cells (PBMC) at single cell (sc) resolution is well described, but little is understood about the cis-regulatory mechanism behind scPBMC gene expression. Here, we profiled the open chromatin landscape of porcine PBMC using single nucleus ATAC sequencing (snATAC-seq). Approximately 22% of the identified peaks overlapped with annotated transcription start sites (TSS). Using clustering based on open chromatin pattern similarity, we demonstrate that cell type annotations using snATAC-seq are highly concordant to that reported for sc RNA sequencing (scRNA-seq). The differentially accessible peaks (DAPs) for each cell type were characterized and the pattern of accessibility of the DAPs near cell type markers across cell types was similar to that of the average gene expression level of corresponding marker genes. Additionally, we found that peaks identified in snATAC-seq have the potential power to predict the cell type specific transcription starting site (TSS). We identified both transcription factors (TFs) whose binding motif were enriched in cell type DAPs of multiple cell types and cell type specific TFs by conducting transcription factor binding motif (TFBM) analysis. Furthermore, we identified the putative enhancer or promoter regions bound by TFs for each differentially expressed gene (DEG) having a DAP that overlapped with its TSS by generating cis-co-accessibility networks (CCAN). To predict the regulators of such DEGs, TFBM analysis was performed for each CCAN. The regulator TF-target DEG pair predicted in this way was largely consistent with the results reported in the ENCODE Transcription Factor Targets Dataset (TFTD). This snATAC-seq approach provides insights into the chromatin accessibility landscape of porcine PBMCs and enables discovery of TFs predicted to control DEG through binding regulatory elements whose chromatin accessibility correlates with the DEG promoter region.
RnaBench: A Comprehensive Library forIn SilicoRNA Modelling
Authors: Runge Frederic , Farid Karim , Franke Jörg K.H. , Hutter Frank 
Published: January 2024

ABSTRACTRNA is a crucial regulator in living organisms and malfunctions can lead to severe diseases. To explore RNA-based therapeutics and applications, computational structure prediction and design approaches play a vital role. Among these approaches, deep learning (DL) algorithms show great promise. However, the adoption of DL methods in the RNA community is limited due to various challenges. DL practitioners often underestimate data homologies, causing skepticism in the field. Additionally, the absence of standardized benchmarks hampers result comparison, while tackling low-level tasks requires significant effort. Moreover, assessing performance and visualizing results prove to be non-trivial and task-dependent. To address these obstacles, we introduce RnaBench (RnB), an open-source RNA library designed specifically for the development of deep learning algorithms that mitigate the challenges during data generation, evaluation, and visualization. It provides meticulously curated homology-aware RNA datasets and standardized RNA benchmarks, including a pioneering RNA design benchmark suite featuring a novel real-world RNA design problem. Furthermore, RnB offers baseline algorithms, both existing and novel performance measures, as well as data utilities and a comprehensive visualization module, all accessible through a user-friendly interface. By leveraging RnB, DL practitioners can rapidly develop innovative algorithms, potentially revolutionizing the field of computational RNA research.
Multiscale characterization of the mechanics of curved fibered structures with application to biological materials
Authors: Sanz-Herrera J.A. , Apolinar-Fernandez A. , Jimenez-Aires A. , Perez-Alcantara P. , Dominguez J. , Reina-Romo E. 
Published: January 2024

AbstractCurved fibered structures are ubiquitous in nature and this organization is found in the majority of biological tissues. Indeed, the mechanical behavior of these materials is of pivotal importance in biomechanics and mechanobiology fields. In this paper, we develop a multiscale formulation to characterize the macroscopic mechanical nonlinear behavior from the microstructure of fibered matrices. From the analysis of the mechanics of a randomly curved single fiber, a fibered matrix model is built to determine the macroscopic behavior following a homogenization approach. The model is tested for tensile, compression and shear loads in a number of applications reminiscent to collagen extracellular matrices. However, any other fibered microstructures can be studied following the proposed formulation. The presented approach naturally recovers instabilities at compression as well as the strain stiffening regime, which are observed experimentally in the mechanical behavior of collagen matrices. Indeed, it was found that the bending energy associated to fiber unrolling, is the most important source of energy developed by fibers for the analyzed cases in tensile and shear in all deformation regions (except the strain stiffening region), whereas bending energy dominates at compression too during buckling. The proposed computational framework can also be used to perform multiscale simulations in the referred applications. As a result, the developed methodology may be an interesting and complementary tool to characterize the nonlinear behavior and evolution of curved fibered structures present in biology and engineered materials.
Mind the instructions: reward cues are liked first, wanted later
Authors: Prutean Nicoleta , Vermeylen Luc , Kukkonen Nanne , Steendam S. Tabitha , Eayrs Joshua O. , Krebs Ruth M. , Wiersema Jan R. , Vassena Eliana , Boehler C. Nico , Notebaert Wim 
Published: January 2024

AbstractCurrent theories propose that mental effort is invested only when the anticipated benefits, such as rewards, outweigh the associated costs, like task difficulty. Yet, it remains unclear whether this motivational and mitigating aspect of reward processing is reflected in the evaluation of reward/difficulty cues as such, and to what extent it depends on task experience. In a pre-registered experiment (N=84), we used the affect misattribution procedure (AMP) to gauge affective evaluations of nonword cues predicting reward and task difficulty levels. Contrary to previous studies, the AMP was administered at the outset, after cue instructions, and after the cues were used in a random dot motion (RDM) task. Compared to baseline, cues predicting a larger reward were evaluated more positively after RDM task experience, and most importantly, already after cue instructions, with no difference between the two phases. This evaluative effect manifested in increased performance after larger reward cues in the RDM task. Our results suggest that AMP effects may generally capture performance expectations which are independent of task experience. Importantly, these instructed expectations of reward and difficulty play a crucial role in the evaluation and subsequent investment of mental effort.
Polygenic risk for schizophrenia converges on alternative polyadenylation as molecular mechanism underlying synaptic impairment
Authors: Raabe Florian J. , Hausruckinger Anna , Gagliardi Miriam , Ahmad Ruhel , Almeida Valeria , Galinski Sabrina , Hoffmann Anke , Weigert Liesa , Rummel Christine K. , Murek Vanessa , Trastulla Lucia , Jimenez-Barron Laura , Atella Alessia , Maidl Susanne , Menegaz Danusa , Hauger Barbara , Wagner Eva-Maria , Gabellini Nadia , Kauschat Beate , Riccardo Sara , Cesana Marcella , Papiol Sergi , Sportelli Vincenza , Rex-Haffner Monika , Stolte Sebastian J. , Wehr Michael C. , Salcedo Tatiana Oviedo , Papazova Irina , Detera-Wadleigh Sevilla , McMahon Francis J , Schmitt Andrea , Falkai Peter , Hasan Alkomiet , Cacchiarelli Davide , Dannlowski Udo , Nenadić Igor , Kircher Tilo , Scheuss Volker , Eder Matthias , Binder Elisabeth B. , Spengler Dietmar , Rossner Moritz J. , Ziller Michael J. 
Published: January 2024

AbstractSchizophrenia (SCZ) is a genetically heterogenous psychiatric disorder of highly polygenic nature. Correlative evidence from genetic studies indicate that the aggregated effects of distinct genetic risk factor combinations found in each patient converge onto common molecular mechanisms. To prove this on a functional level, we employed a reductionistic cellular model system for polygenic risk by differentiating induced pluripotent stem cells (iPSCs) from 104 individuals with high polygenic risk load and controls into cortical glutamatergic neurons (iNs). Multi-omics profiling identified widespread differences in alternative polyadenylation (APA) in the 3’ untranslated region of many synaptic transcripts between iNs from SCZ patients and healthy donors. On the cellular level, 3’APA was associated with a reduction in synaptic density of iNs. Importantly, differential APA was largely conserved between postmortem human prefrontal cortex from SCZ patients and healthy donors, and strongly enriched for transcripts related to synapse biology. 3’APA was highly correlated with SCZ polygenic risk and affected genes were significantly enriched for SCZ associated common genetic variation. Integrative functional genomic analysis identified the RNA binding protein and SCZ GWAS risk gene PTBP2 as a critical trans-acting factor mediating 3’APA of synaptic genes in SCZ subjects. Functional characterization of PTBP2 in iNs confirmed its key role in 3’APA of synaptic transcripts and regulation of synapse density. Jointly, our findings show that the aggregated effects of polygenic risk converge on 3’APA as one common molecular mechanism that underlies synaptic impairments in SCZ.
Key determinants of CRISPR/Cas9 induced inversions in tomato
Authors: Grubben Jillis , Bijsterbosch Gerard , Visser Richard G.F. , Schouten Henk J. 
Published: January 2024

AbstractInversions in chromosomes occur widely within plants and suppress meiotic recombination which can be beneficial or detrimental for plant breeders. Therefore, induction or reversion of inversions via CRISPR/Cas9 has been extensively researched recently. Extensive variation in inversion induction rates and sizes have been reported, from hundreds to several million base pairs. Here, we dissect the influential factors of inversion induction efficiency using CRISPR/Cas9. By using a fixed reference gRNA, we could directly correlate gRNA mutation frequency to inversion frequency and inversion size, of inversions up to 37.5 Mb in length in tomato. Our findings indicate that the least efficient gRNA is the bottleneck for inversion induction, with inversion size having no significant influence unless the inversions were larger than 1 Mb in size. For these huge inversions, the frequency dropped astoundingly, regardless of the gRNA cutting efficiencies. We hypothesize anin plantayet unknown variant of non-homologous-end-joining (NHEJ)-based repair which utilizes active transport of damaged chromosomal sections to dedicated repair sites in the cell nucleus, where repair is finalized. We propose that large inversions are formed less frequently because the transport of these segments to the repair sites may be hampered by their sheer size.
User-friendly Oblique Plane Microscopy on a fully functional commercially available microscope base
Authors: Sirinakis George , Allgeyer Edward S. , Nashchekin Dmitry , St Johnston Daniel 
Published: January 2024

AbstractIn this work we present an Oblique Plane Microscope designed to work seamlessly with a commercially available microscope base. To support all the functionality offered by the microscope base, where the position of the objective lens is not fixed, we adopted a two-mirror scanning geometry that can compensate for changes to the position of the objective lens during routine microscope operation. We showed that within the expected displacement range of the 100X, 1.35 NA objective lens away from its designed position, and for most practical applications, there is no significant effect on the resolving power, or the fidelity of the 3D data produced by the microscope. Compared to the more traditional scan-lens/galvo-mirror combination, the two-mirror scanning geometry offers higher light-efficiency and a more compact footprint, which could be beneficial to all OPM designs regardless of the use of a commercial base or not.
Vestibular prepulse inhibition of the human blink reflex
Authors: Ciocca Matteo , Hosli Sarah , Hadi Zaeem , Mahmud Mohammad , Tai Yen , Seemungal Barry M 
Published: January 2024

AbstractObjectiveAuditory and somatosensory prepulses are commonly used to assess prepulse inhibition (PPI). The effect of a vestibular prepulse upon blink reflex (BR) excitability has not been hitherto assessed.MethodsTwenty-two healthy subjects and two patients with bilateral peripheral vestibular failure took part in the study. Whole body yaw rotation in the dark provided a vestibular inertial prepulse. BR was electrically evoked after the end of the rotation. The area-under-the-curve (area) of the BR responses (R1, R2, and R2c) was recorded and analysed.ResultsA vestibular prepulse inhibited the R2 (p < 0.001) and R2c area (p < 0.05). Increasing the angular acceleration did not increase the R2/R2c inhibition (p>0.05). Voluntary suppression of the vestibular-ocular reflex did not affect the magnitude of inhibition (p>0.05). Patients with peripheral vestibular failure did not show any inhibition.ConclusionsOur data support a vestibular-gating mechanism in humans.SignificanceThe main brainstem nucleus mediating PPI – the pedunculopontine nucleus (PPN) – is heavily vestibular responsive, which is consistent with our findings of a vestibular-mediated PPI. Our technique may be used to interrogate the fidelity of brain circuits mediating vestibular-related PPN functions. Given the PPN’s importance in human postural control, our technique may also provide a neurophysiological biomarker of balance.HighlightsThis is the first report of a vestibular prepulse inhibition of the blink reflex.A vestibular prepulse inhibits the R2/R2c area in healthy subjects but not in patients with bilateral peripheral vestibular failure.Vestibular PPI is a potential neurophysiological marker of vestibular-motor integration at the brainstem level.
Emergence of multiple spontaneous coherent subnetworks from a single configuration of human connectome-coupled oscillators model
Authors: Torres Felipe A. , Otero Mónica , Lea-Carnall Caroline , Cabral Joana , Weinstein Alejandro , El-Deredy Wael 
Published: January 2024

AbstractLarge-scale brain models with biophysical or biophysically inspired parameters generate brain-like dynamics with multi-state metastability. Multi-state metastability reflects the capacity of the brain to transition between different network configurations and cognitive states in response to changing environments or tasks, thus relating to cognitive flexibility. To study this phenomenon, we used a Kuramoto network of oscillators corresponding to a human brain atlas of 90 nodes, each with an intrinsic frequency of 40 Hz. The network’s nodes were interconnected based on the structural connectivity strengths and delays found in the human brain. We identified global coupling and delay scale parameters corresponding to maximum spectral entropy, a proxy for maximal multi-state metastability. At this point, we show that multiple coherent (functional) sub-networks spontaneously emerge across multiple oscillatory modes, and persist in time for periods between 140 and 4389 ms. Most nodes in the network exhibit broad frequency spectra away from their intrinsic frequency, and switch between modes, in a manner similar to that reported in empirical resting-state neuroimaging data. We suggest that the obtained dynamics at maximum metastability is a suitable model of the awake brain. Further, we show that global coupling and delay scale parameters away from maximum metastability yield dynamical features similar to other brain states such as sleep and anesthesia. Therefore, spectral entropy also correlates with wakefulness and the synchrony of functional networks.
The INO80 chromatin remodeling complex regulates histone H2A.Z mobility and the G1-S transition in oligodendrocyte precursors
Authors: Wright Jordan L , Jiang Yi , Nayar Stuart , Rajeeve Vinothini , Cutillas Pedro R , Li Huiliang , Richardson William D 
Published: January 2024

SUMMARYChromatin remodelling complexes (CRCs) participate in oligodendrocyte (OL) differentiation, survival and maintenance. We asked whether CRCs also control proliferation of OL precursors (OPs) – focusing on the INO80 complex, which is known to regulate proliferation of a variety of other cell types during development and disease. CRISPR/Cas9-mediated inactivation ofIno80in vitro, or Cre-mediated deletion in vivo, slowed the OP cell cycle substantially by prolonging G1, without inducing OL differentiation. RNAseq analysis revealed that E2F target genes were dysregulated in OPs from INO80-deficient mice, but correlated RNAseq and ATAC-seq uncovered no general correlation beween gene expression and altered nucleosome positioning at transcription start sites. Fluorescence photobleaching experiments in cultured OPs demonstrated that histone H2A.Z mobility increased following loss of INO80, suggesting that INO80 regulates the cell cycle machinery in OPs through H2A.Z/ H2A exchange. We also present evidence that INO80 associates with OLIG2, a master regulator of OL development.
Production of biologically active human basic Fibroblast Growth Factor (hFGFb) usingNicotiana tabacumtransplastomic plants
Authors: Müller Carolina , Budnik Nicolás , Mirkin Federico Gabriel , Vater Catalina Francisca , Bravo-Almonacid Fernando Félix , Perez-Castro Carolina , Wirth Sonia Alejandra , Segretin María Eugenia 
Published: January 2024

AbstractThe use of plants as biofactories presents as an attractive technology with the potential to efficiently produce high-value human recombinant proteins in a cost-effective manner. Plastid genome transformation stands out for its possibility to accumulate recombinant proteins at elevated levels. Of particular interest are recombinant growth factors, given their applications in animal cell culture and regenerative medicine. In this study we produced recombinant human Fibroblast Growth Factor (rhFGFb), a crucial protein required for animal cell culture, in tobacco chloroplasts. We successfully generated two independent transplastomic lines that are homoplasmic and accumulate rhFGFb in their leaves. Furthermore, the produced rhFGFb demonstrated its biological activity by inducing proliferation in HEK293T cell lines. These results collectively underscore plastid genome transformation as a promising plant-based bioreactor for rhFGFb production.Main conclusionWe generated transplastomic tobacco lines that stably express a human Basic Fibroblast Growth Factor (hFGFb) in their chloroplasts stroma and purified a biologically active recombinant hFGFb.