bluuebunny/crossref_metadata_2025_split huggingface dataset:
RE2DC: a robust and efficient 2D classifier with visualization for processing massive and heterogeneous cryo-EM data
Authors: Chung Szu-Chi , Lin Hsin-Hung , Wu Kuen-Phon , Chen Ting-Li , Chang Wei-Hau , Tu I-Ping 
Published: November 2022

AbstractDespite the fact that single particle cryo-EM has become a powerful method of structural biology, processing cryo-EM images are challenging due to the low SNR, high-dimension and un-label nature of the data. Selecting the best subset of particle images relies on 2D classification—a process that involves iterative image alignment and clustering. This process, however, represents a major time sink, particularly when the data is massive or overly heterogeneous. Popular approaches to this process often trade its robustness for efficiency. Here, we introduced a new unsupervised 2D classification method termed RE2DC. It is built upon a highly efficient variant ofγ-SUP, a robust statistical cryo-EM clustering algorithm resistant to the attractor effect. To develop this efficient variant, we employed a tree-based approximation to reduce the computation complexity fromO(N2) toO(N), withNas the number of images. In addition, we exploited t-SNE visualization to unveil the process of 2D classification. Our tests of RE2DC using various datasets demonstrate it is both robust and efficient, with the potential to reveal subtle structural intermediates. Using RE2DC to curate a dataset of sub-millions of COVID-19 spike particles picked from 3,511 movies only takes 8 hours, suggesting its capability of accelerating cryo-EM structural determination. Currently, RE2DC is available with both CPU and GPU versions, where the implementation only requires modest hardware resources.
Terraces in Species Tree Inference from Gene Trees
Authors: Habib Mursalin , Roy Kowshic , Hasan Saem , Rahman Atif Hasan , Bayzid Md. Shamsuzzoha 
Published: November 2022

AbstractA terrace in a phylogenetic tree space is a region where all trees contain the same set of subtrees, due to certain patterns of missing data among the taxa sampled, resulting in an identical optimality score for a given data set. This was first investigated in the context of phylogenetic tree estimation from sequence alignments using maximum likelihood (ML) and maximum parsimony (MP). The concept of terraces was later extended to the species tree inference problem from a collection of gene trees, where a set of equally optimal species trees was referred to as a “pseudo” species tree terrace. Pseudo terraces do not consider the topological proximity of the trees in terms of the induced subtrees resulting from certain patterns of missing data. In this study, we mathematically characterize species tree terraces and investigate the mathematical properties and conditions that lead multiple species trees to induce/display an identical set of locus-specific subtrees owing to missing data. We report that species tree terraces are agnostic to gene tree topologies and the discordance therein. Therefore, we introduce and characterize a special type of gene tree topology-aware terrace which we call “peak terrace”, and investigate conditions on the patterns of missing data that give rise to peak terraces. In addition to the theoretical and analytical results, we empirically investigated different challenges as well as various opportunities pertaining to the multiplicity of equally good species trees in terraced landscapes. Based on an extensive experimental study involving both simulated and real biological datasets, we present the prevalence of species tree terraces and the resulting ambiguity created for tree search algorithms. Remarkably, our findings indicate that the identification of terraces and the trees within them can substantially enhance the accuracy of summary methods. Furthermore, we demonstrate that reasonably accurate branch support can be computed by leveraging trees sourced from these terraces.
Stretch-activated ion channel TMEM63B associates with developmental and epileptic encephalopathies and progressive neurodegeneration
Authors: Vetro Annalisa , Balestrini Simona , Pelorosso Cristiana , Masi Alessio , Hambleton Sophie , Argilli Emanuela , Conti Valerio , Giubbolini Simone , Barrick Rebekah , Bergant Gaber , Writzl Karin , Bijlsma Emilia K. , Brunet Theresa , Cacheiro Pilar , Mei Davide , Devlin Anita , Hoffer Mariëtte J.V. , Machol Keren , Mannaioni Guido , Sakamoto Masamune , Menezes Manoj P. , Courtin Thomas , Sherr Elliott , Parra Riccardo , Richardson Ruth , Roscioli Tony , Scala Marcello , Stülpnagel Celina von , Smedley Damian ,   TMEM63B collaborators,   The Genomics England Research Consortium, Torella Annalaura , Tohyama Jun , Koichihara Reiko , Hamada Keisuke , Ogata Kazuhiro , Suzuki Takashi , Sugie Atsushi , van der Smagt Jasper J. , van Gassen Koen , Valence Stephanie , Vittery Emma , Kato Mitsuhiro , Matsumoto Naomichi , Ratto Gian Michele , Guerrini Renzo 
Published: November 2022

AbstractBy converting physical forces into electrical signals or triggering intracellular cascades, stretch-activated ion channels (SACs) allow the cell to respond to osmotic and mechanical stress. Knowledge of the pathophysiological mechanisms underlying associations of SACs with human disease is limited. Here we describe 16 unrelated patients, with severe early onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment, associated with progressive neurodegenerative brain changes, carrying ten distinctde novovariants ofTMEM63B, encoding for a highly conserved SAC. Variants were missense, including the recurrent V44M in 7/16 patients, or in-frame, and affected conserved residues located in transmembrane regions of the protein. In 12 patients, haematological abnormalities co-occurred, such as macrocytosis and haemolysis, requiring blood transfusions in some. We modelled V44M, R443H, and T481N in transfected Neuro2a cells and demonstrated leak inward cation currents across the mutated channel even in isotonic conditions, while the response to hypo-osmotic challenge was impaired, as were the Ca2+transients generated under hypo-osmotic stimulation. Ectopic expression of the V44M and G580C variants inDrosophilaresulted in early death.TMEM63B-associated DEE represents a novel clinicopathological entity in which altered cation conductivity results in a severe neurological phenotype with progressive brain damage and early onset epilepsy, associated with haematological abnormalities in most patients.
Systematic violations of patients’ rights and safety: Forced medication of a cohort of 30 patients in Alaska
Authors: Tasch Gail , Gøtzsche Peter C 
Published: November 2022

AbstractWe assessed the records for 30 consecutive petitions for mental health commitment in which an involuntary medication order was requested from Anchorage, Alaska. In 29 cases, the commitment petition was granted. One patient requested a jury trial and the jury found in her favor. The forced medication order was granted in 27 of the 30 cases. In 26 cases, in violation of previous Supreme Court rulings, the patients’ desires, fears, wishes and experiences were totally ignored even when the patients were afraid that the drugs used for psychosis might kill them or when they had experienced serious harms such as tardive dyskinesia. The ethical and legal imperative of offering a less intrusive treatment was ignored. Benzodiazepines were not offered. Psychotherapy was not offered or mentioned in fifteen of the 30 cases. The providers claimed it does not work, even though that statement is blatantly false. The legal procedures can best be characterized as a sham where the patients are defenseless. The power imbalance and abuse were extreme and several of the psychiatrists who argued for forced treatment obtained court orders for administering drugs and dosages that were dangerous. Forced medication should be abandoned.
Plant-TFClass: a structural classification for plant transcription factors
Authors: Blanc-Mathieu Romain , Dumas Renaud , Turchi Laura , Lucas Jérémy , Parcy François 
Published: November 2022

AbstractTranscription factors (TFs) bind DNA at specific sequences to regulate gene expression. This universal process is achieved thanks to the DNA-binding domain (DBD) present in each TF. DBDs show a vast diversity of protein folds within and across organisms, ranging from simple long basic alpha helices to complex structural combinations of alpha, beta and loop folds. In mammals, the structural conformation of the DBDs and the way it establishes contact with DNA has been used to organize TFs in a hierarchical classification named TFClass. However, such classification is missing from plants that possess many DBD types absent from mammals. Here, we reviewed the numerous TF DBD 3D-structures and models available for plants to organize all plant TFs types following the TFClass hierarchy (Superclass/Class/Family/Subfamily). We classified most of the 55 recognized plant TF types within the existing TFClass framework. This extended classification led us to add six new classes and 34 new families corresponding to TF DBD structures absent in mammals. Plant-TFClass provides a unique resource for TF and TF binding sites comparison across TF families and across organisms.
Plasmodium exoerythrocytic parasites redirect trafficking of human proteins to the parasitophorous vacuole
Authors: Calla Jaeson , Mittal Nimisha , LaMonte Greg , Liffner Benjamin , Godinez-Macias Karla P. , Carolino Krypton , Walker Gregory T. , Zou Bing Yu , Paytas Emma , Guerra Layné , Tong-Rios Carlos , Campo Brice , Vinetz Joseph M. , Gamboa Dionicia , Raffatellu Manuela , Absalon Sabrina , Winzeler Elizabeth A. 
Published: November 2022

AbstractChanges in host cell morphology and transcription after apicomplexan parasite infection have long been noted, but there have been few studies of the functional consequences of host cell remodeling. Here we show, using time-dependent immunofluorescence microscopy of multiple human cell lines (HepG2, HC-04, Huh7.5.1 and primary human hepatocytes), infected with multiplePlasmodiumspecies (Plasmodium berghei, P. falciparumandP. vivax(hypnozoites and schizonts)), and antibodies to multiple human proteins (HsNR4A3, HsMUC13, HsGOLGA8A, HsCGA, HsBiP, HsCXCL2), that human protein trafficking is extensively modified inPlasmodiuminfected cells. Using conventional as well as ultrastructure expansion microscopy we show that newly-synthesized human proteins are trafficked to the parasitophorous vacuole instead of the infected-cell plasma membrane, nucleus or extracellular space. Universal redirection of human signaling proteins cells the parasitophorous vacuole may provide a mechanistic explanation for how apicomplexan parasites can block host cells response to infection.
Recording animal-view videos of the natural world
Authors: Vasas Vera , Lowell Mark C. , Villa Juliana , Jamison Quentin D. , Siegle Anna G. , Katta Pavan Kumar Reddy , Bhagavathula Pushyami , Kevan Peter G. , Fulton Drew , Losin Neil , Kepplinger David , Salehian Shakiba , Forkner Rebecca E. , Hanley Daniel 
Published: November 2022

AbstractPlants, animals, and fungi display a rich tapestry of colors. Animals, in particular, use colors in dynamic displays performed in spatially complex environments. In such natural settings, light is reflected or refracted from objects with complex shapes that cast shadows and generate highlights. In addition, the illuminating light changes continuously as viewers and targets move through heterogeneous, continually fluctuating, light conditions. Although traditional spectrophotometric approaches for studying colors are objective and repeatable, they fail to document this complexity. Worse, they miss the temporal variation of color signals entirely. Here, we introduce hardware and software that provide ecologists and filmmakers the ability to accurately record animal-perceived colors in motion. Specifically, our Python codes transform photos or videos into perceivable units (quantum catches) for any animal of known photoreceptor sensitivity. We provide the plans, codes, and validation tests necessary for end-users to capture animal-view videos. This approach will allow ecologists to investigate how animals use colors in dynamic behavioral displays, the ways natural illumination alters perceived colors, and other questions that remained unaddressed until now due to a lack of suitable tools. Finally, our pipeline provides scientists and filmmakers with a new, empirically grounded approach for depicting the perceptual worlds of non-human animals.
Drivers of mangrove vulnerability and resilience to tropical cyclones in the North Atlantic Basin
Authors: do Amaral Cibele Hummel , Poulter Benjamin , Lagomasino David , Fatoyinbo Temilola , Taillie Paul , Lizcano Gil , Canty Steven , Herrera Silveira Jorge Alfredo , Teutli-Hernández Claudia , Cifuentes Miguel , Charles Sean Patrick , Moreno Claudia Shantal , González-Trujillo Juan David , Roman-Cuesta Rosa Maria 
Published: November 2022

AbstractThe North Atlantic Basin (NAB) is seeing a significant increase in the frequency and intensity of tropical cyclones since the 1980s, with record-breaking seasons such as 2017 and 2020. However, little is known about how coastal ecosystems, particularly mangroves in the Gulf of Mexico and the Caribbean, are responding to these new “climate normals” at regional and subregional scales. Wind speed, rainfall, pre-cyclone forest structure, and hydro-geomorphology are known to influence mangrove damage and recovery following cyclones in the NAB. However, these studies have focused on site-specific responses and individual cyclonic events. Here, we analyze 25 years (1996-2020) of mangrove vulnerability (damage after a cyclone) and short-term resilience (recovery after damage) for the entire NAB and its subregions, using multi-annual, remote sensing-derived databases. We applied machine learning to characterize the influence of 22 potential drivers that include previously researched variables and new ones such as human development and long-term climate trends. The characteristics of the cyclones mainly drive vulnerability at the regional level, while resilience is largely driven by site-specific conditions. These include long-term climate conditions, such as air temperature and drought trends, pre-cyclone habitat conditions, such as canopy cover and height and soil organic carbon stock, and human interventions on the land. Rates and drivers of mangrove vulnerability and resilience vary across subregions in the NAB, and hotspots for restoration and conservation actions are highlighted within subregions. The impacts of increasing cyclone activity need to be framed in the context of climate change compound effects and heavy human influences in the region. There is an urgent need to value the restoration and conservation of mangroves as fundamental Nature-based Solutions against cyclone impacts in the NAB.
Phylogenomics reveals extensive misidentification of fungal strains from the genusAspergillus
Authors: Steenwyk Jacob L. , Balamurugan Charu , Raja Huzefa A. , Gonçalves Carla , Li Ningxiao , Martin Frank , Berman Judith , Oberlies Nicholas H. , Gibbons John G. , Goldman Gustavo H. , Geiser David M. , Hibbett David S. , Rokas Antonis 
Published: November 2022

AbstractModern taxonomic classification is often based on phylogenetic analyses of a few molecular markers, although single-gene studies are still common. However, the use of one or few molecular markers can lead to inaccurate inferences of species history and errors in classification. Here, we leverage genome-scale molecular phylogenetics (phylogenomics) of species and populations to reconstruct evolutionary relationships in a dense dataset of 711 fungal genomes from the biomedically and technologically important genusAspergillus. To do so, we generated a novel set of 1,362 high-quality molecular markers specific forAspergillusand provide profile Hidden Markov Models for each, facilitating others to use these molecular markers. Examination of the resulting genome-scale phylogeny: (1) helped resolve ongoing taxonomic controversies and identified new ones; (2) revealed extensive strain misidentification, underscoring the importance of population-level sampling in species classification; and (3) identified novel lineages that may shed light on the early evolution of an important genus. These findings suggest that phylogenomics of species and populations can facilitate accurate taxonomic classifications and reconstructions of the tree of life.
Tau pathology in the dorsal raphe may be a prodromal indicator of Alzheimer’s disease
Authors: Pierson Samantha , Fiock Kimberly L. , Wang Ruixiang , Balasubramanian Nagalakshmi , Reindhardt Jessica , Khan Kanza M. , James Thomas D. , Betters Ryan , Deniz Kaancan , Lee Gloria , Aldridge Georgina , Hefti Marco M. , Marcinkiewcz Catherine A. 
Published: November 2022

ABSTRACTProtein aggregation in brainstem nuclei is thought to occur in the early stages of Alzheimer’s disease (AD), but its specific role in driving prodromal symptoms and disease progression is largely unknown. The dorsal raphe nucleus (DRN) contains a large population of serotonin (5-hydroxytryptamine; 5-HT) neurons that regulate mood, reward-related behavior, and sleep, which are all disrupted in AD. We report here that tau pathology is present in the DRN of individuals 54-80 years old without a known history of dementia and was found at higher frequency than α-synuclein and TDP-43. Most AD cases had tau pathology in the DRN (90%), whereas only a subset contained TDP-43 or α-synuclein, but not both (30%). To evaluate how early tau pathology impacts behavior, we overexpressed human P301L-tau in the DRN of mice and observed depressive-like behaviors and hyperactivity without any deficits in spatial memory. Tau pathology was predominantly found in neurons relative to glia and colocalized with a significant proportion of Tph2-expressing neurons in the DRN. 5-HT neurons were also hyperexcitable in P301L-tauDRNmice, and there was an increase in the amplitude of excitatory post-synaptic currents (EPSCs), suggestive of increased glutamatergic transmission. Moreover, astrocytic density was elevated in the DRN and accompanied by an increase in IL-1α and Frk expression, which is indicative of inflammation. Additionally, tau pathology was detected in axonal processes in the thalamus, hypothalamus, amygdala, and caudate putamen and a significant proportion of this tau pathology colocalized with the serotonin reuptake transporter (SERT), suggesting that tau may spread in an anterograde manner to regions outside the DRN. Together these results indicate that tau pathology accumulates in the DRN in a subset of individuals over 50 years and may lead to behavioral dysregulation, 5-HT neuronal dysfunction, and activation of local astrocytes which may be prodromal indicators of AD.
Tissue microenvironment dictates the state of human induced pluripotent stem cell-derived endothelial cells of distinct developmental origin in 3D cardiac microtissues
Authors: Cao Xu , Mircea Maria , van den Hil Francijna E. , Mei Hailiang , Neumann Katrin , Anastassiadis Konstantinos , Mummery Christine L. , Semrau Stefan , Orlova Valeria V. 
Published: November 2022

ABSTRACTEach tissue and organ in the body has its own type of vasculature. Here we demonstrate that organotypic vasculature for the heart can be recreated in a three-dimensional cardiac microtissue (MT) model composed of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), cardiac fibroblasts (CFs) and endothelial cells (ECs). ECs in cardiac MTs upregulated expression of markers enriched in human intramyocardial ECs (iECs), such asCD36, CLDN5, APLNR, NOTCH4, IGFBP3, ARHGAP18, which were previously identified in the single-cell RNA-seq dataset from the human fetal heart (6.5-7 weeks post coitum). We further show that the local microenvironment largely dictates the organ-specific identity of hiPSC-derived ECs: we compared ECs of different developmental origins derived from two distinct mesoderm subtypes (cardiac and paraxial mesoderm) and found that independent of whether the ECs were cardiac or paraxial mesoderm derived, they acquired similar identities upon integration into cardiac microtissues. This was confirmed by single-cell RNA-seq. Overall, the results indicated that whilst the initial gene profile of ECs was dictated by developmental origin, this could be modified by the local tissue environment such that the original identity was lost and the organotypic identity acquired through local environmental signals. This developmental “plasticity” in ECs has implications for multiple pathological and disease states.
IMPASTO: Multiplexed cyclic imaging without signal removalviaself-supervised neural unmixing
Authors: Kim Hyunwoo , Bae Seoungbin , Cho Junmo , Nam Hoyeon , Seo Junyoung , Han Seungjae , Yi Euiin , Kim Eunsu , Yoon Young-Gyu , Chang Jae-Byum 
Published: November 2022

AbstractSpatially resolved proteomics requires a highly multiplexed imaging modality. Cyclic imaging techniques, which repeat staining, imaging, and signal erasure, have been adopted for this purpose. However, due to tissue distortion, it is challenging to obtain high fluorescent signal intensities and complete signal erasure in thick tissue with cyclic imaging techniques. Here, we propose an “erasureless” cyclic imaging method named IMPASTO. In IMPASTO, specimens are iteratively stained and imaged without signal erasure. Then, images from two consecutive rounds are unmixed to retrieve the images of single proteins through self-supervised machine learning without any prior training. Using IMPASTO, we demonstrate 30-plex imaging from brain slices in 10 rounds, and when used in combination with spectral unmixing, in five rounds. We show that IMPASTO causes negligible tissue distortion and demonstrate 3D multiplexed imaging of brain slices. Further, we show that IMPASTO can shorten the signal removal processes of existing cyclic imaging techniques.
CASBERT: BERT-Based Retrieval for Compositely Annotated Biosimulation Model Entities
Authors: Munarko Yuda , Rampadarath Anand , Nickerson David P. 
Published: November 2022

ABSTRACTMaximising FAIRness of biosimulation models requires a comprehensive description of model entities such as reactions, variables, and components. The COmputational Modeling in BIology NEtwork (COMBINE) community encourages the use of RDF with composite annotations that semantically involve ontologies to ensure completeness and accuracy. These annotations facilitate scientists to find models or detailed information to inform further reuse, such as model composition, reproduction, and curation. SPARQL has been recommended as a key standard to access semantic annotation with RDF, which helps get entities precisely. However, SPARQL is not suitable for most repository users who explore biosimulation models freely without adequate knowledge regarding ontologies, RDF structure, and SPARQL syntax. We propose here a text-based information retrieval approach, CASBERT, that is easy to use and can present candidates of relevant entities from models across a repository’s contents. CASBERT adapts Bidirectional Encoder Representations from Transformers (BERT), where each composite annotation about an entity is converted into an entity embedding for subsequent storage in a list-like structure. For entity lookup, a query is transformed to a query embedding and compared to the entity embeddings, and then the entities are displayed in order based on their similarity. The simple list-like structure makes it possible to implement CASBERT as an efficient search engine product, with inexpensive addition, modification, and insertion of entity embedding. To demonstrate and test CASBERT, we created a dataset for testing from the Physiome Model Repository and a static export of the BioModels database consisting of query-entities pairs. Measured using Mean Average Precision and Mean Reciprocal Rank, we found that our approach can perform better than the traditional bag-of-words method.